Showing papers in "Diabetes Care in 1994"

Obesity, Fat Distribution, and Weight Gain as Risk Factors for Clinical Diabetes in Men

Abstract: OBJECTIVE To investigate the relation between obesity, fat distribution, and weight gain through adulthood and the risk of non-insulin-dependent diabetes melli-tus (NIDDM). RESEARCH DESIGN AND METHODS We analyzed data from a cohort of 51,529 U.S. male health professionals, 40-75 years of age in 1986, who completed biennial questionnaires sent out in 1986, 1988, 1990, and 1992. During 5 years of follow-up (1987-1992), 272 cases of NIDDM were diagnosed among men without a history of diabetes, heart disease, and cancer in 1986 and who provided complete health information. Relative risks (RRs) associated with different anthropometrie measures were calculated controlling for age, and multivariate RRs were calculated controlling for smoking, family history of diabetes, and age. RESULTS We found a strong positive association between overall obesity as measured by body mass index (BMI) and risk of diabetes. Men with a BMI of ≥35 kg/m 2 had a multivariate RR of 42.1 (95% confidence interval [CI] 22.0-80.6) compared with men with a BMI 2 . BMI at age 21 and absolute weight gain throughout adulthood were also significant independent risk factors for diabetes. Fat distribution, measured by waist-to-hip ratio (WHR), was a good predictor of diabetes only among the top 5%, while waist circumference was positively associated with the risk of diabetes among the top 20% of the cohort. CONCLUSIONS These data suggest that waist circumference may be a better indicator than WHR of the relationship between abdominal adiposity and risk of diabetes. Although early obesity, absolute weight gain throughout adulthood, and waist circumference were good predictors of diabetes, attained BMI was the dominant risk factor for NIDDM; even men of average relative weight had significantly elevated RRs.

A Practical Two-Step Quantitative Clinical and Electrophysiological Assessment for the Diagnosis and Staging of Diabetic Neuropathy

Abstract: OBJECTIVE Early diagnosis of distal symmetric sensorimotor polyneuropathy, a common complication of diabetes, may decrease patient morbidity by allowing for potential therapeutic interventions. We have designed an outpatient program to facilitate diagnosis of diabetic neuropathy. RESEARCH DESIGN AND METHODS Patients are initially administered a brief questionnaire and screening examination, designated the Michigan Neuropathy Screening Instrument (MNSI). Diabetic neuropathy is confirmed in patients with a positive assessment by a quantitative neurological examination coupled with nerve conduction studies, designated the Michigan Diabetic Neuropathy Score (MDNS). In this study, 56 outpatients with confirmed type I or II diabetes were administered the standardized quantitative components required to diagnose and stage diabetic neuropathy according to the San Antonio Consensus Statement (1) and the Mayo Clinic protocol (2). These same patients were then assessed with the MNSI and the MDNS. RESULTS Of 29 patients with a clinical MNSI score > 2, 28 had neuropathy. Twenty-eight patients with an MDNS of ≥ 7 had neuropathy, while 21 non-neuropathic patients had a score ≤ 6. Of 35 patients with diabetic neuropathy, 34 had ≥ 2 abnormal nerve conductions. Twenty-one normal patients and one patient with neuropathy had ≤ 1 abnormal nerve conduction. CONCLUSIONS The results indicate that the MNSI is a good screening tool for diabetic neuropathy and that the MDNS coupled with nerve conductions provides a simple means to confirm this diagnosis.

Frequency of severe hypoglycemia in patients with type I diabetes with impaired awareness of hypoglycemia.

Abstract: OBJECTIVE To determine the frequency of hypoglycemia in patients with type I diabetes and impaired awareness of hypoglycemia by prospective assessment. RESEARCH DESIGN AND METHODS A prospective study was undertaken for 12 months in 60 patients with type I diabetes: 29 had impaired awareness of hypoglycemia and 31 retained normal awareness of hypoglycemia. The two groups of patients were matched for age, age at onset of diabetes, duration of diabetes, and glycemic control. Episodes of severe hypoglycemia were recorded within 24 h of the event and verified where possible by witnesses. RESULTS During the 12 months, 19 (66%) of the patients with impaired awareness had one or more episodes of severe hypoglycemia with an overall incidence of 2.8 episodes · patient –1 ·year –1 . By comparison, 8 (26%) of the patients with normal awareness experienced severe hypoglycemia ( P –1 · year –1 ( P P = 0.03), and patients with normal awareness experienced a greater proportion in the early morning ( P = 0.05). An assessment of fear of hypoglycemia revealed that patients with impaired awareness of hypoglycemia worried more about hypoglycemia than did patients with normal awareness ( P = 0.008), but did not modify their behavior accordingly. CONCLUSIONS This prospective evaluation demonstrated that impaired awareness of hypoglycemia predisposes to a sixfold increase in the frequency of severe hypoglycemia, much of which occurred at home during waking hours.

The Prediction of Diabetic Neuropathic Foot Ulceration Using Vibration Perception Thresholds: A prospective study

Abstract: OBJECTIVE To assess the ability of vibration perception threshold (VPT) to predict the development of diabetic foot ulceration. RESEARCH DESIGN AND METHODS A prospective follow-up study of consecutive patients with vibration perception measured by biothesiometry from April 1988 to March 1989. Patients were stratified in various risk groups. RESULTS Patients with a VPT 25 V, odds ratio (OR) 7.99 (3.65–17.5, 95% confidence intervals), P < 0.01. The incidence of ulceration increased with duration of diabetes, but even with this effect removed, the excess of ulceration persisted, OR 6.82 (2.75–16.92), P < 0.01. CONCLUSIONS VPT is an effective predictor of the risk of foot ulceration in diabetes and therefore could be used to target foot-care education to those patients most likely to benefit and, thereby, possibly improve its effectiveness.

The evaluation of two measures of quality of life in patients with type I and type II diabetes

Abstract: OBJECTIVE To examine the effects of type I and type II diabetes on patient perceptions of their quality of life and compare the psychometric properties of a generic versus a diabetes-specific quality of life measure. RESEARCH DESIGN AND METHODS Consecutive outpatients ( n = 240) from a large multispecialty diabetes clinic were studied on a single occasion using two measures of quality of life—Diabetes Quality of Life Measure (DQOL) and the Medical Outcome Study Health Survey 36-Item Short Form (SF-36). No interventions were performed. This study examines three issues: 1 ) the reliability(internal consistency) of the two measures; 2 ) the relationship between the DQOL and SF-36 scales; and 3 ) the influence of clinical patient characteristics, such as number and severity of diabetes complications, on quality of life. Examination of this issue provides information about the construct validity of the two quality of life measures. RESULTS The estimates of internal consistency (Cronbach9s alpha) for the DQOL and SF-36 subscales ranged from 0.47 to 0.97. These values werevery similar to the published findings from previous studies. The subscales of the two measures were variably correlated with one another (range of correlations: —0.003 to 0.60), indicating that the areas of functioning addressed by the DQOL and SF-36 overlapped only to a modest degree. Examination of the relationship of demographic factors to the DQOL measures suggests that they are not generally confounded by factors such as education, sex, or duration of diabetes. Health-related quality of life is affected by the marital status of both type I and type II diabetic patients, with separated and divorced individuals generally experiencing lower levels of quality of life. The quality of life measures were sensitive to clinical characteristics, such as frequency and severity of complications. Even after factors such as marital status and, among type II diabetic patients, type of treatment, patients9 severity of diabetes complications was a significant predictor of both the diabetes-related and the more broad-based measure of quality of life. For type II diabetic patients, insulin treatment was associated with lower levels of satisfaction with diabetes and greater impact of diabetes on quality of life. CONCLUSIONS This study provides evidence for the reliability and validity of two measures of quality of life. The two measures examine quality of life from different but complimentary perspectives. The DQOL seems more sensitive to lifestyle issues and contains special questions and worry scales oriented toward younger patients, whereas the SF-36 provides more information about functional health status. Thus, the measures may be used usefully in combination in studies of both type I and type II diabetic patients.

Cow's milk exposure and type I diabetes mellitus. A critical overview of the clinical literature

Abstract: OBJECTIVE To critically review and summarize the clinical evidence relating a short duration of breast-feeding or early cow9s milk exposure to insulin-dependent (type I) diabetes. RESEARCH DESIGN AND METHODS All relevant citations retrieved through comprehensive searching of the medical literature were critically reviewed and analyzed. Those case-control studies that minimized the possibility of bias were meta-analyzed to determine overall odds ratios (ORs) and 95% confidence intervals (CIs). RESULTS Ecological and time-series studies consistently showed a relationship between type I diabetes and either cow9s milk exposure or diminished breast-feeding. In the case-control studies, patients with type I diabetes were more likely to have been breast-fed for CONCLUSIONS Early cow9s milk exposure may be an important determinant of subsequent type I diabetes and may increase the risk ∼1.5 times.

A Mathematical Model for the Determination of Total Area Under Glucose Tolerance and Other Metabolic Curves

Abstract: OBJECTIVE To develop a mathematical model for the determination of total areas under curves from various metabolic studies. RESEARCH DESIGN AND METHODS In Tai's Model, the total area under a curve is computed by dividing the area under the curve between two designated values on the X-axis (abscissas) into small segments (rectangles and triangles) whose areas can be accurately calculated from their respective geometrical formulas. The total sum of these individual areas thus represents the total area under the curve. Validity of the model is established by comparing total areas obtained from this model to these same areas obtained from graphic method Gess than ±0.4%). Other formulas widely applied by researchers under- or overestimated total area under a metabolic curve by a great margin. RESULTS Tai's model proves to be able to 1 ) determine total area under a curve with precision; 2 ) calculate area with varied shapes that may or may not intercept on one or both X/Y axes; 3 ) estimate total area under a curve plotted against varied time intervals (abscissas), whereas other formulas only allow the same time interval; and 4 ) compare total areas of metabolic curves produced by different studies. CONCLUSIONS The Tai model allows flexibility in experimental conditions, which means, in the case of the glucose-response curve, samples can be taken with differing time intervals and total area under the curve can still be determined with precision.

Effects of a Traditional Lifestyle on Obesity in Pima Indians

Abstract: OBJECTIVE The Pima Indians of Arizona have the highest reported prevalences of obesity and non-insulin-dependent diabetes mellitus (NIDDM). In parallel with abrupt changes in lifestyle, these prevalences in Arizona Pimas have increased to epidemic proportions during the past decades. To assess the possible impact of the environment on the prevalences of obesity and NIDDM, data were collected on members of a population of Pima ancestry (separation 700–1,000 years ago) living in a remote mountainous location in northwestern Mexico, with a lifestyle contrasting markedly with that in Arizona. RESEARCH DESIGN AND METHODS Pima heritage was established by history and by use of Pima language. Measurements of weight, height, body fat (bio-impedance), blood pressure, plasma levels of glucose, cholesterol, and HbA1c were obtained in 19 women (36 ±13 years of age) and 16 men (48 ±14 years of age) and compared with sex-, age- and diabetes status-matched Pimas living in Arizona (10 Arizona Pimas for each Mexican Pima). RESULTS Mexican Pimas were lighter (64.2 ± 13.9 vs. 90.2 ± 21.1 kg, P < 0.0001; means ± SD) and shorter (160 ± 8 vs. 164 ± 8 cm, P < 0.01) with lower body mass indexes (24.9 ± 4.0 vs. 33.4 ± 7.5 kg/m2, P < 0.0001) and lower plasma total cholesterol levels (146 ± 30 vs. 174 ± 31 mg/dl, P < 0.0001) than Arizona Pimas. Only two women (11%) and one man (6%) had NIDDM, contrasting with the expected prevalences of 37 and 54% in female and male Arizona Pimas, respectively. CONCLUSIONS This preliminary investigation shows that obesity, and perhaps NIDDM, is less prevalent among people of Pima heritage living a “traditional” lifestyle than among Pimas living in an “affluent” environment. These findings suggest that, despite a similar potential genetic predisposition to these conditions, a traditional lifestyle, characterized by a diet including less animal fat and more complex carbohydrates and by greater energy expenditure in physical labor, may protect against the development of cardiovascular disease risk factors, obesity, and NIDDM.

Therapeutic Comparison of Metformin and Sulfonylurea, Alone and in Various Combinations: A double-blind controlled study

Abstract: OBJECTIVE To assess and compare the therapeutic efficacy and safety of metformin (M) and sulfonylurea (glyburide, G), alone and in various combinations, in patients with non-insulin-dependent diabetes mellitus (NIDDM). RESEARCH DESIGN AND METHODS Of 165 patients (fasting blood glucose [FBG] ≥ 6.7 mmol/l) initially treated with diet alone, 144 (FBG still ≥6.7 mmol/l) were randomized to double-blind, double-dummy controlled treatment with M, G, or primary combination therapy (MG). The dose was titrated, withFBG RESULTS The FBG target was achieved in 9% of patients after diet alone. Single-drug therapy was insufficient in 36% and MGL in 25% (NS) of the randomized patients. There was further improvement in glucose control by the high-dose combinations. Mean FBG ± SE was reduced ( P = 0.001) from 9.1 ± 0.4 to 7.0 ± 0.2 mmol/l in those maintained on single-drug treatment or low-dose primary combination. Those treated with different high-dose combinations had a large mean FBG reduction, from 13.3 ± 0.8 to 7.8 ± 0.6 mmol/l. HbA 1c levels showed corresponding reductions, and glycemic levels rose after drug discontinuation. Fasting C-peptide rose during treatment with G and MGL but not with M, while fasting insulin was not significantly changed. Meal-stimulated C-peptide and insulin levels were unchanged by M but increased by G and, to a lesser extent, by MGL. There were no significant insulin or C-peptide differences between the different high-dose combinations (M/G, G/M, and MGH). Body weight did not change following treatment with M or combination but increased by 2.8 ± 0.7 kg following G alone. Blood pressure was unchanged. Overall effects on plasma lipids were small, with no significant differences between groups. Drug safety was satisfactory, even if the reporting of (usually modest) adverse events was high; the profile, but not the frequency, differed between groups. CONCLUSIONS Dose-effect titrated treatment with either metformin or glyburide promotes equal degrees of glycemic control. The former, but not the latter, is able to achieve this control without increasing body weight or hyperinsulinemia. Near-normal glycemia can be obtained by a combination of metformin and sulfonylurea, even in advanced NIDDM.

Muscle Fiber Composition and Capillary Density in Women and Men With NIDDM

Abstract: OBJECTIVE To determine whether muscle fiber composition and capillary density differed between diabetic and nondiabetic subjects. RESEARCH DESIGN AND METHODS Muscle fiber composition and capillary density were determined in biopsies from women and men with non-insulindependent diabetes mellitus (NIDDM) and compared with those of control subjects matched for gender, age, obesity, and the waist-to-hip ratio, which are all factors known to influence muscle morphology. RESULTS Patients with NIDDM, as well as control subjects with abdominal obesity and insulin resistance, showed the same abnormalities in muscle morphology, namely, a low percentage of type I fibers, elevated type II (particularly type IIB) fibers, and a low capillary density. These changes correlated closely with insulin concentrations in both diabetic and nondiabetic groups. CONCLUSIONS Recent information suggests that insulin may regulate myosin synthesis in muscle in the direction of the changes observed. Therefore, it is possible that muscle fiber composition abnormalities in insulin-resistant conditions are secondary to hyperinsulinemia. However, the low capillary density, hypothetically, may contribute to insulin resistance.

Preventive Eye Care in People With Diabetes Is Cost-Saving to the Federal Government: Implications for health-care reform

Abstract: OBJECTIVE Diabetic retinopathy, which leads to macular edema and retinal neovascularization, is the leading cause of blindness among working-age Americans. Previous research has demonstrated significant cost savings associated with detection of eye disease in Americans with type 1 diabetes. However, detection and treatment of eye disease among those with type II diabetes was previously thought not to be cost-saving. Our purpose was to estimate the current and potential federal savings resulting from the screening and treatment of retinopathy in patients with type II diabetes, based on recently availabledata concerning efficacy of treating both macular edema and neovascularization along withnew data on federal budgetary costs of blindness. RESEARCH DESIGN AND METHODS We used computer modeling, incorporating data from population-based epidemiological studies and multicenter clinical trials. Monte Ciarlosimulation was used, combined with sensitivity analysis and present value analysis of cost savings. RESULTS Screening and treatment for eye disease in patients with type II diabetes generates annual savings of $247.9 million to the federal budget and 53,986 person-years of sight, even at current suboptimal (60%) levels of care. If all patients with type II diabetes receive recommended care, the predicted net savings (discounted at 5%) exceeds $472.1 million and 94,304 person-years of sight. Nearly all savings areassociated with detection and treatment of diabetic macular edema. Enrolling each additional person with type II diabetes into currently recommended ophthalmological care resultsin an average net savings of $975/person, even if all costs of care are borne by the federal government. CONCLUSIONS Our analysis indicates that prevention programs aimed at improving eye care for patients with diabetes not only reduce needless vision loss but also willprovide a financial return on the investment of public funds.

Light-to-Moderate Alcohol Intake Is Associated With Enhanced Insulin Sensitivity

Abstract: OBJECTIVE To test the hypothesis that insulin-mediated glucose uptake is enhanced in light-to-moderate alcohol consumption. RESEARCH DESIGN AND METHODS This is a case-control study of healthy volunteers, divided into nondrinkers and light-to-moderate drinkers based on their history of alcohol consumption. The study was performed at the General Clinical Research Center at Stanford University Medical Center and involved 40 volunteers, 20 men and 20 women. Measurements were made of the plasma glucose and insulin responses to an oral glucose challenge, fasting plasma lipid and lipoprotein concentrations, and steady-state plasma insulin (SSPI) and steady-state plasma glucose (SSPG) concentrations in response to a continuous infusion of somatostatin, insulin, and glucose. RESULTS Light-to-moderate drinkers (10-30 g/day) had lower integrated plasma glucose (17.8 ± 0.8 vs. 19.8 ± 0.9 mM/h, P P P ± 0.02). Despite similar SSPI concentrations of ∼300 pM, SSPG concentrations were lower ( P ± 0.01) in light-to-moderate drinkers (6.7 ± 0.8 vs. 10.7 ± 1.2 mM). Results were independent of age, body mass index, ratio of waist-to-hip girth, and estimates of level of habitual physical activity. CONCLUSIONS Light-to-moderate alcohol consumption in healthy men and women is associated with enhanced insulin-mediated glucose uptake, lower plasma glucose and insulin concentrations in response to oral glucose, and a higher HDLcholesterol concentration. The changes in glucose and insulin metabolism may contribute to the lower risk of coronary heart disease described in light-to-moderate drinkers.

Postural instability in patients with diabetic sensory neuropathy.

Abstract: OBJECTIVE Recent survey evidence suggests that sensory ataxia due to diabetic neuropathy may be a more frequent and serious problem than is commonly recognized. This view is further supported by research that confirms the major contribution of the somatosensory system to the control of posture. We therefore sought to determine the effects of significant diabetic distal symmetrical polyneuropathy on the control of posture. RESEARCH DESIGN AND METHODS Fifty-one subjects, divided into three groups, participated in this study. Seventeen had diabetes and significant sensory neuropathy, 17 had diabetes and no neuropathy, and 17 had neither diabetes nor neuropathy. The subjects were matched across groups, and stringent exclusion criteria were applied. Postural stability during quiet standing was measured using a force platform. In addition to electrophysiological and quantitative sensory tests of neuropathy, a number of physical and functional characteristics were measured for all subjects. RESULTS Postural instability was found to be significantly associated with sensory neuropathy, but not with diabetes per se. Patients with sensory neuropathy demonstrated between 66 and 117% more instability than did control subjects (depending on the testing condition). Based on multiple linear regression analyses, the most significant correlates of instability were the quantitative sensory measures of neuropathy and age. CONCLUSIONS The loss of sensory perception secondary to diabetic distal symmetrical sensory neuropathy has a markedly detrimental effect on postural stability. The deficit is greatest when visual or vestibular cues are absent or degraded. Patients with neuropathy need to be informed of the postural consequences of this condition to limit the potential morbidity caused by falls.

Caloric Restriction Per Se Is a Significant Factor in Improvements in Glycemic Control and Insulin Sensitivity During Weight Loss in Obese NIDDM Patients

Abstract: OBJECTIVE To examine the effects of caloric restriction, independent of differences in weight loss, on improvements in glycemic control, fasting insulin, and insulin sensitivity. RESEARCH DESIGN AND METHODS We randomized 93 obese type II diabetic patients to two different degrees of calorie restriction (1,674 or 4,185 kJ/day; 400 or 1,000 kcal/day) and compared the changes in fasting glucose, fasting insulin, and insulin sensitivity that resulted from a comparable reduction in body weight (11% of initial body weight). Insulin sensitivity was assessed using the minimal model analysis of frequently sampled intravenous glucose tolerance tests. RESULTS Despite equal weight losses, subjects in the 1,674 kJ/day (400 kcal) condition had lower fasting glucose levels (7.61 vs. 10.13 mM, P = 0.03) and greater insulin sensitivity (1.79 vs. 1.13, P = 0.04) after weight loss than did subjects in the 4,185 kJ/day (1,000 calorie) condition. Subjects were restudied 15 weeks later when both groups were consuming a 4,185 kJ/day (1,000 kcal/day) diet. Subjects who increased from 1,674 to 4,185 kJ (400 to 1,000 calories) had worse fasting glycemic control in spite of continued weight loss, whereas subjects who remained on 4,185 kJ (1,000 calories) throughout had further improvements in both blood glucose and insulin sensitivity with increased weight loss. CONCLUSIONS Both degree of calorie restriction and magnitude of weight loss have independent effects on improvements in glycemic control and insulin sensitivity.

Smoking is associated with progression of diabetic nephropathy.

Abstract: OBJECTIVE To investigate the association between cigarette smoking and the progression of diabetic nephropathy. RESEARCH DESIGN AND METHODS A prospective, follow-up study over one year was conducted in a sequential sample of 34 smokers, 35 nonsmokers, and 24 ex-smokers with type I diabetes, hypertension, and diabetic nephropathy. Progression of renal disease was defined according to the stage of nephropathy as an increase in proteinuria or serum creatinine or a decrease in the glomerular filtration rate. RESULTS Progression of nephropathy was less common in nonsmokers (11%) than in smokers (53%) and patients who had quit smoking (33%), P > 0.001. In a stepwise logistic regression analysis, cigarette pack years, 24-h sodium excretion, and GHb were independent predictive factors for the progression of diabetic nephropathy. Because blood pressure (BP) was well controlled in these patients and most values were within a normotensive range, neither standing, sitting, nor supine BP values were associated with progression of nephropathy. CONCLUSIONS Cigarette smoking represents an important factor associated with progression of nephropathy in treated hypertensive type I diabetic patients.

Insulin Omission in Women With IDDM

Abstract: OBJECTIVE To describe the extent of intentional insulin omission in an outpatient population of women with insulin-dependent diabetes mellitus (IDDM) and examine its relationship to disordered eating, attitudes toward diabetes, other psychosocial factors, long-term complications, and glycemic control. RESEARCH DESIGN AND METHODS Before their routinely scheduled clinic appointments, female IDDM patients who were 13–60 years of age completed a self-report survey (final n = 341). The survey included standardized questionnaires assessing disordered eating attitudes and behaviors, psychological functioning (general distress, diabetes-specific distress, and hypoglycemic fear), attitudes toward diabetes, and self-care behaviors. All subjects were assessed for glycosylated hemoglobin within 30 days of survey completion. Long-term complications were determined through chart review. RESULTS Approximately 31% of the subject sample, representing women of all ages, reported intentional insulin omission, but only 8.8% reported frequent omission. Compared with non-omitters, omitters reported more disordered eating, greater psychological distress (general and diabetes-specific), more hypoglycemic fear, poorer regimen adherence, and greater fears concerning improved diabetes management (which may lead to weight gain). Omitters evidenced poorer glycemic control, more diabetes-related hospitalizations, and higher rates of retinopathy and neuropathy. Multivariate examination revealed only two variables that independently predicted omission: diabetes-specific distress and fear of improved glycemic control (“because I will gain weight”). Of the omitters, approximately half reported omitting insulin for weight-management purposes (weight-related omitters). These subjects evidenced significantly greater psychological distress, poorer regimen adherence (including more frequent omission), poorer glycemic control, and higher rates of complications than did non-weight-related omitters as well as non-omitters. Non-weight-related omitters tended to fall between weight-related omitters and non-omitters on most measures of psychological functioning, adherence, and glycemic control. CONCLUSIONS These findings suggest that insulin omission is common, that it is not limited to younger women, and that the medical consequences of omission, especially frequent omission, may be severe. Although a strong association between omission and disordered eating was observed, these data suggest that this link may be complicated by important diabetes-specific factors. Patients preoccupied with eating and weight concerns may also become emotionally overwhelmed by diabetes and/or fearful of normoglycemia (and the associated weight-related consequences), thus reinforcing the desire to omit insulin and maintain elevated blood glucose levels.

Testosterone concentrations in women and men with NIDDM.

Abstract: OBJECTIVE To evaluate androgen concentrations in relation to insulin resistance in men and women with and without NIDDM. Recent studies have indicated the potential importance of the regulation of insulin sensitivity by androgens in both women and men. Low sex hormone binding globulin (SHBG) concentration is an independent risk factor for the development of non-insulin-dependent diabetes mellitus (NIDDM) in women and is strongly associated statistically with signs of insulin resistance. RESEARCH DESIGN AND METHODS We compared measurements of anthropometric variables and SHBG, steroid hormone, and insulin concentrations of women and men who have NIDDM with those of control subjects. RESULTS Women with NIDDM had somewhat higher plasma insulin concentrations, lower SHBG, and higher free testosterone values than did control subjects with similar body mass index (BMI). Women with NIDDM had marginally higher waist-to-hip ratios (WHR). Plasma insulin concentrations correlated positively with BMI, WHR, and free testosterone and negatively with SHBG. In multivariate analyses, insulin concentrations remained positively associated with BMI and free testosterone. Men with NIDDM had higher fasting plasma insulin concentrations than did the nondiabetic control subjects. Testosterone and SHBG were lower in the diabetic men than in both control groups. The derived value of free testosterone was not different between groups. Univariate correlation analyses revealed tight statistical couplings between plasma insulin on the one hand and SHBG and testosterone concentrations (negative) on the other. In multivariate analyses, only the insulin-testosterone association remained. CONCLUSIONS Women with NIDDM have high levels of free testosterone and low levels of SHBG. Insulin resistance is closely correlated with these signs of hyperandrogenicity as well as with obesity. Men with NIDDM also have low levels of SHBG and, in contrast to women, low testosterone values. Insulin values correlate negatively with these hormonal factors. Based on the results of experimental work and intervention studies, we suggest that these androgen abnormalities might be causally related to insulin resistance in NIDDM.

Which left ventricular function is impaired earlier in the evolution of diabetic cardiomyopathy? An echocardiographic study of young type I diabetic patients.

Abstract: OBJECTIVE To determine whether diastolic dysfunction preceded systolic dysfunction in the evolution of diabetic cardiopathy. RESEARCH DESIGN AND METHODS A total of 157 young (mean age 26.6 years) cardiac asymptomatic type 1 diabetic patients and 54 age- and sex-matched healthy (nondiabetic) subjects were studied. The severity of diabetic complications (retinopathy, nephropathy, and cardiac autonomic neuropathy) was evaluated by the diabetic complication index (DCl), a sum of individual scores for each complication. Left ventricular (LV) function was studied by M-mode echocardiography. Impaired systolic and diastolic functions were presumed if at least two echocardiographic variables for systolic function (fractional shortening [FS], mean velocity of circumference fiber shortening, and stroke index) and for diastolic function (slope of anterior mitral leaflet in early diastole, isovolumic relaxation time [IRT], and left atrium emptying index) were out of the control range (mean ± 2 SD). RESULTS Diastolic dysfunction was twice as common as systolic dysfunction (27% and 12%, respectively, P P P > 0.05). Diastolic dysfunction, represented by the interval from minimal LV dimension to mitral valve opening, was seen in diabetic patients ∼8 years after onset of diabetes and systolic dysfunction represented by FS after ∼18 years. Diastolic dysfunction, represente by 1RT, was found in the presence of mild complications (DCl = 2), and systolic dysfunction, represented by FS, was found in the presence of more severe complications (DCl = 4). CONCLUSIONS Our findings indicate that myocardial damage in patients with diabetes affects diastolic function before systolic function. The intentional assessment of diastolic function is advisable for early detection of LV dysfunction before clinical symptoms appear, with follow-up to detect further deterioration of cardiac status.

Dietary fat predicts conversion from impaired glucose tolerance to NIDDM. The San Luis Valley Diabetes Study.

Abstract: This decade will bring major changes to the therapy of diabetes. New drugs are likely to include monomeric insulins, fatty-acid-oxidation inhibitors, insulin-secretion inducers, and nutrition modifiers. Likely new devices include improved insulin pens, less invasive methods of insulin administration, and noninvasive blood glucose monitoring. The use of computers will integrate this care, and artificial intelligence will provide new approaches to all of health care. An integrated system for using these new technologies, such as staged diabetes management, will ensure an orderly, cost-effective transition in therapy by the entire health-care community.

Nutrition principles for the management of diabetes and related complications.

Abstract: Health professionals and people with diabetes recognize nutrition therapy as one of the most challenging aspects of diabetes care and education (1). Adherence to meal planning principles requires the person with diabetes to learn specific nutrition recommendations. It may require altering previous patterns of eating and implementing new eating behaviors, which requires motivation for a healthy lifestyle and may also require participation in exercise programs. Finally, individuals must be able to evaluate the effectiveness of these lifestyle changes. Despite these challenges, nutrition is an essential component of successful diabetes management.

Weight Loss in Severely Obese Subjects Prevents the Progression of Impaired Glucose Tolerance to Type II Diabetes: A longitudinal interventional study

Abstract: OBJECTIVE To determine if weight loss may prevent conversion of impaired glucose tolerance (IGT) to diabetes, because weight loss reduces insulin resistance. The prevalence of IGT in the U. S. population is estimated at 11.2%, more than twice that of diabetes. Furthermore, because an oral glucose tolerance test is needed for its detection, most of these patients are undiagnosed. Screening for IGT would be meaningful if progression to diabetes could be delayed or prevented. RESEARCH DESIGN AND METHODS For an average of 5.8 years (range 2–10 years), 136 individuals with IGT and clinically severe obesity (>45 kg excess body weight) were followed. The experimental group included 109 patients with IGT who underwent bariatric surgery for weight loss. The control group was made up of 27 subjects with IGT who did not have bariatric surgery. The criteria of the World Health Organization was used to detect IGT and diabetes in this population. The main outcome measure of this nonrandomized control trial is the incidence density, or number of events (development of diabetes) divided by the time of exposure to risk. RESULTS Of the 27 subjects in the control group, 6 developed diabetes during an average of 4.8 ± 2.5 years of postdiagnosis follow-up, yielding a rate of conversion to diabetes of 4.72 cases per 100 person-years. The 109 individuals of the experimental group were followed for an average of 6.2 ± 2.5 years postbariatric surgery. Based on the 95% confidence interval of the comparison group, we would expect to find that between 22 and 36 subjects in the experimental group developed diabetes over the follow-up period. Only 1 of the 109 experimental-group patients developed diabetes, resulting in a conversion rate of the experimental group of only 0.15 cases per 100 person-years, which is significantly lower ( P CONCLUSIONS Weight loss in patients with clinically severe obesity prevents the progression of IGT to diabetes by >30-fold.

Self-monitoring of blood glucose

Abstract: your blood glucose levels? Diabetes is a complex condition that differs from patient to patient. It is important that you monitor your glucose levels regularly and get familiar with your pattern of readings at different times of the day. Regular self-monitoring provides valuable information that your health care team can use to make decisions about medication and insulin and improve control of your diabetes. Monitoring your blood glucose also helps prevent immediate problems that can result from glucose levels that are too high (hyperglycemia) or too low (hypoglycemia). Both conditions can be serious if not treated right away.

Subcutaneous Injection of the Incretin Hormone Glucagon-Like Peptide 1 Abolishes Postprandial Glycemia in NIDDM

Abstract: OBJECTIVE To investigate the effect of subcutaneously injected glucagon-like peptide 1 (GLP-1) (7–36)amide on postprandial plasma glucose, insulin, and C-peptide levels in patients with non-insulin-dependent diabetes mellitus (NIDDM) and a secondary failure to sulfonylureas. RESEARCH DESIGN AND METHODS GLP-1 (25 nmol) was injected subcutaneously into either the abdominal wall or the gluteal region at a standardized depth and speed. The injection device was guided by the ultrasound determination of the depth of the fat layer. The peptide was given 5 min before a standard meal. Plasma concentrations of glucose, C-peptide, insulin, glucagon, and GLP-1 were followed during 240 min after the injection. RESULTS In control experiments, a significant hyperglycemia was attained after the meal. GLP-1 given into the abdominal wall not only virtually abolished the postprandial blood glucose rise but significantly decreased glucose concentrations, with a nadir at ∼25 min after the injection. A rapid rise of C-peptide and insulin levels was observed 10-15 min after the injection of GLP-1. The stimulatory effect of GLP-1 was transient, and, at 45 min after the meal, both insulin and C-peptide levels were almost identical in GLP-1 and control experiments. Significantly lower glucagon concentrations were observed 35-65 min after the peptide injection. GLP-1 concentration in plasma increased from 10 pM to a peak concentration ( C max ) of 70 pM at T max 30 min after injection. Then GLP-1 levels rapidly decreased to 25 pM at 95 min and returned to basal at 215 min. The gluteal injection of GLP-1 had similar effects compared with the abdominal administration on plasma levels of glucose, insulin, C-peptide, and glucagon. CONCLUSIONS GLP-1 is promptly absorbed from the subcutaneous tissue. It exerts a significant blood glucose lowering effect when administered before meals in overweight patients with NIDDM.

Exercise in individuals with IDDM.

Abstract: The greater energy requirements that accompany exercise necessitate an increase in fuel mobilization from sites of storage and a subsequent increase in the oxidation of thesefuels within the working muscle. A precise endocrine response controls the needed increment in fuel metabolism. The importance of the endocrine system is readily apparent in individuals with insulin-dependent diabetes mellitus (IDDM) in whom the normal endocrine response to exercise is lost. When a person with IDDM exercises with too little insulin in the circulation, an excessive counterregulatory hormone response may ensue, and the alreadyelevated blood glucose and ketone body levels can become even greater. On the other hand,if too much insulin is present, the exercise-induced increase in substrate mobilization can be attenuated or completely blocked and, as a result, hypoglycemia may ensue. Insulin therapy must be modified in anticipation of exercise to avoid states of under- or overinsulinization, and/or carbohydrate ingestion must be adjusted to compensate for the potential glycemic effects of inappropriate insulin levels. The presence of advanced diabetic complications can further accentuate the difficulty of exercise for those with IDDM. The purpose of this review is to provide the scientific information necessary to assess therationale for recommending regular exercise to individuals with IDDM and to develop guidelines for integrating daily exercise with insulin treatment and dietary management.

Selected vitamins and minerals in diabetes.

Abstract: The interrelationship between diabetes and various vitamins and minerals is characterized by a high degree of reciprocity. Chronic uncontrolled hyperglycemia can cause significant alterations in the status of these nutrients, and conversely, some of these substances, especially those that have been characterized as micronutrients, can directly modulate glucose homeostasis (1). Differences in patient populations studied and methodological uncertainties account for the discrepancies in most reported studies. Certain subgroups of individuals with diabetes, such as elderly patients, vegans (who consume no animal products), and pregnant and lactating women, are at particular risk for deficiencies for such nutrients. Additionally, caloric restriction for obese patients and the effects of a high fiber diet and a host of drugs on the metabolism of vitamins and minerals are of concern (2,3).

Use of fetal ultrasound to select metabolic therapy for pregnancies complicated by mild gestational diabetes.

Abstract: OBJECTIVE To determine whether fetal ultrasound early in the third trimester can identify Latina with mild gestational diabetes mellitus (GDM) whose fetuses are at risk for macrosomia and, if so, whether maternal insulin therapy can reduce that risk. RESEARCH DESIGN AND METHODS Study subjects included 303 consecutive women with GDM and a fasting serum glucose level th percentile for gestational age, and 59 women completed a randomized trial of diet therapy ( n = 29) or diet plus twice daily insulin ( n = 30). Maternal nutrient levels were assessed by meal tolerance testing (MTT) before and during therapy and by capillary glucose monitoring four to seven times a day. Birth weights corrected for gestational age and neonatal glycemia and skin folds were the primary outcome variables compared between treatment groups. RESULTS Diet and diet-plus-insulin groups were well matched for maternal age, prepregnancy relative weight, weight gain during pregnancy, and glycemia at entry. Insulin therapy reduced maternal capillary ( P P P P P P CONCLUSIONS Fetal ultrasound early in the third trimester identified women with mild GDM whose infants were at high risk for fetal macrosomia in the absence of standard glycemic criteria for insulin therapy. Insulin treatment reduced the macrosomia, indicating that fetal ultrasound can be used to guide metabolic therapy in pregnancies complicated by mild GDM.

Stroke in the Diabetic Patient

Abstract: A higher prevalence of stroke is found in the patient with both diagnosed and undiagnosed diabetes and glucose intolerance. Because of local cerebral acidosis caused by ischemia and hyperglycemia, morbidity and mortality from a stroke are increased. Most studies show that individuals with admission serum glucose >120 mg/dl (6.7 mM) have a higher morbidity and mortality from a stroke. The prevalence of cerebral infarcts, especially lacunar infarcts, is increased and the prevalence of subarachnoid hemorrhage, cerebral hemorrhage, and transient ischemie attacks are decreased in the diabetic patient. Age, race, hypertension, and the presence of diabetic nephropathy and coronary and peripheral vascular disease are risk factors for stroke in the diabetic patient, whereas obesity, smoking, hyperlipidemia, and glycemie control are not. Investigation and treatment of the diabetic patient with a stroke is discussed.

Hyperinsulinemia and Macrosomia in the Fetus of the Diabetic Mother

Abstract: OBJECTIVE To determine 1 ) whether macrosomia in the fetus of the diabetic mother is related to fetal hyperinsulinemia and 2 ) whether hyperinsulinemia and macrosomia are related to maternal metabolic control. RESEARCH DESIGN AND METHODS Normal pregnant women ( n = 95) were compared with insulin-treated pregnant women ( n = 155), who were subdivided according to White9s class, hypertension, and mode of delivery. All women were treated to achieve optimal metabolic control. HbA 1c was determined at each visit. At delivery, umbilical plasma was analyzed for glucose, insulin antibodies, total insulin, free insulin, C-peptide, proinsulin components, and total and individual amino acids. RESULTS Macrosomia, defined as CONCLUSIONS Macrosomia in the fetus of the diabetic mother remains inadequately explained. In a large population of pregnant women with strict metabolic control, macrosomia was mainly independent of glycosylated hemoglobin. Nevertheless, fetal hyperinsulinism remains the driving force for excessive fetal growth. The stimulus for fetal insulin excess in humans remains to be defined.

Prevalence of arterial hypertension in diabetic patients before and after the JNC-V.

Abstract: OBJECTIVE To compare the prevalence of arterial hypertension in patients with insulin-dependent diabetes mellitus (IDDM) and non-insulin-dependent diabetes mellitus (NIDDM) according to blood pressure (BP) criteria from the World Health Organization (WHO) and The Fifth Report of the Joint National Committee on Detection, Evaluation and Treatment of High Blood Pressure (JNC-V). RESEARCH DESIGN AND METHODS Two cohorts of Caucasian patients attending the outpatient clinic at Hvidore Hospital were identified: 1) 957 patients with IDDM; 53% men, 40 (18–75) years of age (mean [range]); and 2) 549 patients with NIDDM; 53% men, 60 (20–76) years of age. BP was measured at least yearly, while patients rested in a sitting position, with a standard clinical sphygmomanometer. Patients were classified as hyper- or normotensive based on average BP during a 3-year follow-up period. Patients receiving antihypertensive treatment were classified as hypertensives. RESULTS In IDDM patients, the prevalence of arterial hypertension rose from 15 to 42% in the normoalbuminuric group, from 26 to 52% in the microalbuminuric group, and from 61 to 79% in the macroalbuminuric group when WHO and JNC-V criteria were compared. The corresponding rises in NIDDM patients were from 51 to 71% (normo-), from 73 to 90% (micro-), and from 82 to 93% (macroalbuminuria). Of the untreated hypertensive patients, 78% of IDDM patients and 50% of NIDDM patients had stage 1 (140–159/90–99 mmHg) hypertension; 20% of IDDM patients and 37% of NIDDM patients had stage 2 (160–179/100–109 mmHg) hypertension. Two out of three untreated hypertensive patients had isolated systolic hypertension. CONCLUSIONS The new JNC-V criteria approved by the American Diabetes Association leads to a considerable increase in the prevalence of arterial hypertension in a population of IDDM and NIDDM patients. Isolated systolic hypertension contributes importantly.

Environmental Factors in Childhood IDDM: A population-based, case-control study

Abstract: OBJECTIVE To identify environmental factors involved in the etiology of insulin-dependent diabetes mellitus (IDDM). RESEARCH DESIGN AND METHODS An estimated 90% of all incident cases of IDDM in patients 0–14 years of age in New South Wales, Australia, were ascertained over 18 months. For each IDDM patient, two age- and sex-matched control subjects were randomly selected from the population. Past environmental exposures were determined with a questionnaire completed by the parents. Response rates were 92% for the IDDM patients (217 of 235) and 55% for the control subjects (258 of 470). The relative risk associated with each exposure was estimated with the odds ratio (OR) adjusted for confounding factors using multiple logistic regression. RESULTS The introduction of cow9s milk-based infant formula into the diet before 3 months of age was associated with an increased risk (OR 1.52, 95% confidence interval [CI] 1.04–2.24). Exclusive breast-feeding for ≥3 months was associated with a protective effect (OR 0.66, 95% CI 0.45–0.97). High dietary intake of cow9s milk protein in the 12 months before the onset of diabetic symptoms was also associated with an increased risk (OR 1.84, 95% CI 1.12–3.00). A recent infection (during the 3 months before onset of diabetic symptoms) was more common in the patients than the control subjects (OR 2.92, 95% CI 1.96–4.35), as was day care attendance before the age of 3 (OR 1.73, 95% CI 1.00–3.00). When two age-groups, defined by the median age at onset of diabetes, were compared, the associations with early infant-feeding were stronger among the younger group ( CONCLUSIONS These results indicate an increased risk of IDDM associated with early dietary exposure to cow9s milk-containing formula, short duration of exclusive breast-feeding, high intake of cow9s milk protein in the recent diet, recent infection, and early attendance at day care.