Showing papers in "Diabetes Care in 1987"

Evaluating Clinical Accuracy of Systems for Self-Monitoring of Blood Glucose

Abstract: Although the scientific literature contains numerous reports of the statistical accuracy of systems for self-monitoring of blood glucose (SMBG), most of these studies determine accuracy in ways that may not be clinically useful. We have developed an error grid analysis (EGA), which describes the clinical accuracy of SMBG systems over the entire range of blood glucose values, taking into account 1) the absolute value of the system-generated glucose value, 2) the absolute value of the reference blood glucose value, 3) the relative difference between these two values, and 4) the clinical significance of this difference. The EGA of accuracy of five different reflectance meters (Eyetone, Dextrometer, Glucometer I, Glucometer II, Memory Glucometer II), a visually interpretable glucose reagent strip (Glucostix), and filter-paper spot glucose determinations is presented. In addition, reanalyses of a laboratory comparison of three reflectance meters (Accucheck II, Glucometer II, Glucoscan 9000) and of two previously published studies comparing the accuracy of five different reflectance meters with EGA is described. EGA provides the practitioner and the researcher with a clinically meaningful method for evaluating the accuracy of blood glucose values generated with various monitoring systems and for analyzing the clinical implications of previously published data.

Fear of Hypoglycemia: Quantification, Validation, and Utilization

Abstract: Hypoglycemia can lead to various aversive symptomatic, affective, cognitive, physiological, and social consequences, which in turn can lead to the development of possible phobic avoidance behaviors associated with hypoglycemia. On the other hand, some patients may inappropriately deny or disregard warning signs of hypoglycemia. This study presents preliminary reliability and validity data on a psychometric instrument designed to quantify this fear: the hypoglycemic fear survey. The instrument was found to have internal consistency and test-retest stability, to covary with elevated glycosylated hemoglobin, and to be sensitive to a behavioral treatment program designed to increase awareness of hypoglycemia.

Diabetes Control and Complications Trial (DCCT): Results of feasibility study

Abstract: The Diabetes Control and Complications Trial (DCCT) is a multicenter, randomized, clinical study designed to determine whether an intensive treatment regimen directed at maintaining blood glucose concentrations as close to normal as possible will affect the appearance or progression of early vascular complications in patients with insulin-dependent diabetes mellitus (IDDM). We present the baseline characteristics and 1-yr results of the initial cohort of 278 subjects randomized in phase II of the trial, a phase designed to answer several feasibility questions before initiating a full-scale trial. During phase II, recruitment was completed on schedule. The 191 adults and 87 adolescents were randomized either to standard treatment (90 adults and 42 adolescents), designed to approximate conventional diabetes treatment, or to experimental treatment (101 adults and 45 adolescents), designed to achieve near-normal blood glucose and HbA1c concentrations. With few exceptions, baseline demographic, ophthalmologic, renal, and other medical characteristics were evenly distributed by randomization between the two treatment groups in both age strata. Glycemic control at baseline, as assessed by HbA1c concentrations and by blood glucose profiles, was comparable between the treatment groups in both age strata. The treatment strategies employed produced statistically significant and clinically meaningful differences in HbA1c concentrations and blood glucose profiles between the experimental- and standard-group subjects for both adults and adolescents. These differences were maintained throughout the feasibility phase. Except for an increased incidence of hypoglycemia in the experimental group, the two treatment regimens maintained or improved the clinical well-being of subjects in both groups. Adherence and completeness of follow-up were excellent (>95%), and the methods employed to measure biochemical and pathologic characteristics of IDDM proved to be reliable, reproducible, and precise. The feasibility phase of the DCCT demonstrated that a complex multicenter, randomized study of the relationship between diabetes control and complications can be performed. The full-scale, long-term trial therefore has been initiated.

Self-Efficacy in Adolescent Girls and Boys With Insulin-Dependent Diabetes Mellitus

Abstract: Adolescents with insulin-dependent diabetes mellitus (IDDM) face increasing responsibilities for managing their own treatment. For some, implementing their treatment regimen enhances diabetes self-efficacy beliefs because they welcome the chance to exert control over their illness. Other adolescent patients, however, feel overwhelmed and helpless. We developed the self-efficacy for diabetes scale (SED) with a sample of adolescent boys (n = 34) and girls (n = 34) with IDDM. High reliability (internal consistency) and evidence for criterion validity were obtained for this measure, because SED scores predicted metabolic control. In addition, construct validity was established, because SED scores were related to theoretically relevant measures of locus of control and self-esteem. Although they showed similar expectancies for diabetes self-efficacy, girls had significantly positive correlations between their SED scores and metabolic control, whereas boys did not. We offer a new instrument for studying adolescent patient perceptions and physical health.

Randomized, controlled trial of diabetic patient education: improved knowledge without improved metabolic status.

Abstract: We randomized 749 insulin-treated patients on the rolls of the Mount Sinai Medical Center Diabetes Clinic in a controlled trial of diabetic patient education; 345 agreed to participate, of whom 165 were assigned to the education group and 180 to the control group. Cognitive scores increased from 5.3 +/- 1.6 to 5.8 +/- 1.6 in the education group, but there was no change in the control group, whose score was 5.3 +/- 1.7 before and after the intervention (P = .0073). HbA1c fell from 6.8 +/- 2.1 to 6.1 +/- 2.0% in the education group and from 6.6 +/- 2.0 to 6.3 +/- 2.0% in the control group, an insignificant difference (P = .1995). The fasting blood glucose decreased from 223 +/- 94 to 179 +/- 73 mg/dl in the education group and from 199 +/- 81 to 185 +/- 76 mg/dl in the controls (P = .1983). Triglycerides, high- and low-density lipoprotein cholesterol, and insulin dosage also failed to show significant variation among groups. The foot-lesion score showed similar progression in the education and control groups. Neither diastolic nor systolic blood pressure showed significantly greater change in the education or the control group, with falls noted, particularly in diastolic pressures, in both patient groups. Differences between the groups were not significant for sick days, hospitalizations, emergency room visits, or outpatient visits. The sample sizes of the study and control populations were sufficiently large to detect a difference in means between the education and control groups in the HbA1c, the primary outcome variable, of greater than 1.0%, with alpha = .05 and a power of .95. Thus, our study suggests that patient education may not be an efficacious therapeutic intervention in most adults with insulin-treated diabetes mellitus.

Vibratory and cooling detection thresholds compared with other tests in diagnosing and staging diabetic neuropathy.

Abstract: Increasingly more tests are being used to detect and characterize diabetic polyneuropathy, but their value in setting minimal criteria for the diagnosis of neuropathy and for staging severity remains inadequately studied. In 180 diabetics, we compared the percentage of patients with test abnormalities and associations among test results, evaluating neuropathic symptoms [neuropathy symptom score (NSS) and neuropathy scale of neuropathy symptom profile (NNSP)], deficits [neurologic disability score (NDS) and vibratory (VDT) and cooling (CDT) detection thresholds], or nerve dysfunction [nerve conduction (NC)]. The percentage of patients that were abnormal varied considerably depending on criteria for abnormality and the tests used. Abnormality (≥ 3 SD of 1 or more parameters) of NC of one or more of four nerves occurred in 80%, of two or more in 69%, of three or more in 46%, and of four in 21%. Similarly, for other tests, the rate of abnormality decreased with use of increasingly stringent criteria. Setting the criteria for abnormal NC at abnormality of two or more nerves, NSS at ≥ 1, NDS at > 6, NNSP at ≥ 97.5th percentile, and at ≥ 95th percentile for the other tests, NC was abnormal in 69%, NSS in 54%, NDS in 48%, NNSP in 47%, VDT in 44%, and CDT in 35%. Abnormality of any two or more of the six tests evaluated occurred in 64% of patients. We estimated that at least 16% of patients without abnormal NC (

Postexercise Late-Onset Hypoglycemia in Insulin-Dependent Diabetic Patients

Abstract: A new clinical entity that is prevalent in young type I (insulin-dependent) diabetic patients, postexercise late-onset (PEL) hypoglycemia, is described. A prospective case-finding study suggested that PEL hypoglycemia occurred in 48 of approximately 300 diabetic type I patients who were diagnosed as diabetic before age 20 yr and who were monitored for up to 2 yr. Typically, hypoglycemia was nocturnal and occurred 6-15 h after the completion of unusually strenuous exercise or play. In more than half the cases the hypoglycemia resulted in loss of consciousness or seizures and necessitated treatment with subcutaneous glucagon or intravenous glucose and/or attendance by a health professional. The hypoglycemia was not limited to patients in good or excellent metabolic control and often occurred after a single bout of exercise in patients unaccustomed to exercise or in athletic patients who were making the transition from an untrained to a trained state. Surprisingly, 12 of the patients who experienced nocturnal PEL hypoglycemia were not using significant amounts of insulin that peaked at night. Type I diabetic patients should be made aware of the possibility of PEL hypoglycemia to enable them to make adjustments in their management plans in anticipation of unusually strenuous exercise, so that they may attempt to minimize or avoid late-onset hypoglycemia.

Type II diabetic subjects lose less weight than their overweight nondiabetic spouses

Abstract: To determine whether diabetic individuals have more difficulty losing weight than nondiabetic individuals, 12 overweight diabetic subjects (6 men, 6 women) and their overweight nondiabetic spouses were treated together in a behavioral weight-control program. Diabetic and nondiabetic subjects did not differ in age, weight, or percent overweight. Weight losses of nondiabetic spouses were significantly greater than those of diabetic patients (13.4 +/- 1.7 vs. 7.5 +/- 1.4 kg; P less than .01). Differences emerged by wk 5 and became greater over the 20-wk program. Nondiabetic subjects reduced their intake significantly more than diabetics, suggesting that differences in dietary adherence were responsible for the differences in weight loss.

Single-Void Urine Samples Can Be Used To Estimate Quantitative Microalbuminuria

Abstract: The excretion of small quantities of urinary albumin (microalbuminuria) may predict renal failure in diabetes. The measurement of microalbuminuria with radioimmunoassays has been based on 24-h, overnight, and 3- to 4-h collections. To determine whether single-void urine samples can be used to estimate 24-h excretion, we compared the results of 24-h outpatient urine collections with single-void samples corrected for creatinine from diabetic and nondiabetic subjects. The overall correlation of single-void sample results expressed as microgram albumin per milligram creatinine with 24-h excretion (mg/24 h) was excellent ( r = .82, P < .001). More important, in the diabetic patients the sensitivity and specificity of detecting 24-h microalbuminuria in the abnormal range were at least 94 and 96%, respectively. Single-void urine specimens adjusted for creatinine discriminate between normal and abnormal levels of microalbuminuria, as determined in 24-h urine collection, with high specificity and sensitivity.

Obesity in Offspring of Diabetic Pima Indian Women Despite Normal Birth Weight

Abstract: The relationships of birth weight and maternal diabetes to the development of obesity were examined at 5-19 yr of age in the offspring of Pima Indian women. At each age, offspring of diabetic women, even those who were of normal birth weight, had a higher mean weight relative to height than offspring of nondiabetic and prediabetic women. Birth weight was predictive of relative weight in 5- to 9- and 10- to 14-yr-old offspring of nondiabetic women but not in the oldest group. In contrast, for offspring of prediabetic and diabetic women, birth weight was not predictive of subsequent obesity at any age studied. Offspring of diabetic women were heavier than offspring of nondiabetic and prediabetic women regardless of birth weight. Thus, maternal diabetes was important in predicting body size in the offspring even after accounting for the effects of the birth weight and maternal body size.

Intellectual Deficits Associated With Early Onset of Insulin-Dependent Diabetes Mellitus in Children

Abstract: Twenty-seven children with early-onset (less than 4 yr) diabetes (EOD), 24 children with late-onset (greater than 4 yr) diabetes (LOD), and 30 sibling controls were compared in their performance on tests of intellectual functioning and school achievement. The results indicated that children with EOD, particularly girls, scored lower than the other groups of diabetic children and siblings on tests of visuospatial (P less than .05) but not verbal ability. Many of the girls with EOD were also having difficulty at school, and several were receiving special education. Children with EOD had more hypoglycemic convulsions than those with LOD. Both convulsions and age of onset were associated with poorer performance on spatial tasks. Girls with EOD had lower spatial test scores regardless of convulsion history, whereas boys with EOD scored lower only if they had had a convulsion.

Measurements of glucose control.

Abstract: Among the definitions of the verb control, the following best suits our purposes: \"to exercise restraining or directing influence over, to regulate or curb\" (1). When used in the context of blood glucose, it implies the restraint of disordered glycemic behavior of diabetes by restoration of glucose behavior toward that of the fully controlled or regulated state, i.e., the nondiabetic condition. Although there may be disagreements about the fine points of what constitutes good or bad glucose control, there probably is agreement that perfect glucose control requires achievement of the levels and patterns of glycemia seen in nondiabetic individuals. As is the case in most biological systems, the assessment of glucose control requires objective measurements rather than reliance on subjective symptoms. Techniques for the assessment of glucose control were developed several decades ago to determine the effectiveness of newly developed modified insulin preparations (2-9). Many of these techniques relied on periodic blood glucose measurements and determinations of urine glucose excretion. Although most of these approaches are of historic interest only, the need to measure glucose control is even more pressing today. Assessments of new treatments that have the potential to achieve normoglycemia and the role of glycemia on the degenerative complications of diabetes depend on measurements of glucose control. There are several facets to consider in the measurement of glucose control. J) Glucose behavior may be measured directly by the determination of glucose concentrations in blood or indirectly by measurements of urine glucose or glycosylated proteins. Because of the varying half-lives of these parameters, they provide short-term (e.g., plasma glucose), intermediate-term (e.g., glycosylated albumin, fructosamine), or long-term (e.g., glycosylated hemoglobin) indications of glucose control. 2) Measurement of glucose behavior should not be limited to mean glycemia. Because glycemia is not static but responsive to various stimuli, the pattern of glycemic behavior may have physiologic and pathophysiologic implications. 3) An important component of glucose behavior is the frequency and severity of hypoglycemia. Quantification of hypoglycemia is difficult primarily because of the problems associated with ascertainment. 4) The approach to measuring glucose control differs between clinical and research purposes, because the former requires information to make treatment judgments, whereas the latter requires comprehensive assessment of glucose behavior. 5) Measurement of glucose control varies between inpatient and outpatient settings because of the differences in purposes, in access for frequent blood sampling, and in duration of assessment.

Hyperbaric Oxygen in Diabetic Gangrene Treatment

Abstract: We treated a group of 18 hospitalized adult diabetic patients (all with retinopathy, 17 with symptomatic neuropathy, and 6 with macroangiopathy) presenting with gangrenous lesions of the foot by a combined regime consisting of strict metabolic control, daily debridement of necrotic tissues, and daily hyperbaric oxygen (HBO) treatments given in a multiplace oxygen chamber. Another group of 10 adult subjects with comparable foot lesions (all with retinopathy, 9 with symptomatic neuropathy, and 4 with macroangiopathy) was treated in exactly the same way except for HBO. In the test treatment group, 16 patients were healed, and the remaining 2 showed no improvement and later underwent amputation. The number of HBO treatments required for healing was significantly related to the size of gangrenous lesions. In the non-HBO-treated group, only 1 patient improved, 5 of 10 showed no change, and 4 of 10 worsened until leg amputation was unavoidable. Comparison of the two groups by chi 2-test revealed a highly significant difference (P = .001). In practical terms, HBO treatment drastically reduced leg amputations in patients so treated in the last 3 yr compared with earlier and current figures for patients not receiving HBO treatment.

Model of Associations Between Psychosocial Variables and Health-Outcome Measures of Adolescents with IDDM

Abstract: The purpose of this study was to develop a model that describes the contributions of key psychosocial variables to the health outcome of adolescents with insulin-dependent diabetes mellitus (IDDM). Subjects were 93 adolescents with IDDM and their parents. Health-outcome measures included adherence and metabolic control (HbA 1c ). Psychosocial variables included adolescent age, chronic life stress, social competence, family relations, and family knowledge about IDDM. Multiple regression analyses showed that adherence ( P P P P P 1c and 18.5% of the variance in predicting adherence. In general, these findings are consistent with extant theory. The direct link between stress and metabolic control, however, contrasts with the current view that psychosocial variables affect metabolic control indirectly through their influence on adherence behavior. The methodological limitations of the findings are noted, directions for future research are suggested, and the implications for clinical interventions are described.

Prevalence of Diabetes Mellitus in Rural Saudi Arabia

Abstract: Several studies have clearly shown the impact of modernization on the prevalence of diabetes mellitus in susceptible communities. Saudi Arabia has faced a rapid development program over the last two decades. In a recent study, we found a high prevalence of diabetes mellitus in urban Saudi Arabia. A total of 5222 rural subjects of both sexes were involved in a study of the prevalence of diabetes mellitus in the western region of Saudi Arabia. Random capillary blood glucose, body weight and height, and income were recorded. The results showed an overall prevalence of 4.3%. There was a rise of prevalence with age and higher-income groups. Prevalence also differed with sex. The overall prevalence in women (5.9%) was twice that for men (2.9%; P less than .001). Obesity occurred in 41.2% of our diabetic subjects compared to 29.3% in nondiabetic subjects (P less than .001). Multiple logistic regression analysis with body mass index (BMI) as the dependent variable showed that sex and income status were significant factors (P less than .0001 and P less than .04, respectively). When blood glucose was fixed as the dependent variable, the analysis showed that age, income, and BMI were significant factors (P less than .004, P less than .0001, and P less than .045, respectively).

Ambulatory Glucose Profile: Representation of Verified Self-Monitored Blood Glucose Data

Abstract: Sixty-nine individuals with diabetes (23 with type I, 15 with pregestational, and 31 with gestational) used specially modified reflectance meters containing memory chips enabling the instruments to store 440 individual blood glucose values with corresponding time and date These data were organized into 14-day periods and then collapsed into a graphic depiction, the Ambulatory Glucose Profile (AGP), which was represented as the pattern of the 25th, 50th, and 75th percentiles of blood glucose values These three curves illustrate the median level of control and provide an index of variability in control at each hour of a "typical day" We observed distinctive AGPs related to the variability in metabolic control and the type of diabetes Comparisons between diagnostic groups showed consistent differences between groups, independent of level of glycemic control Review of serial AGPs obtained for sequential 2-wk periods for 23 non-pregnant individuals with type I diabetes and 10 women with gestational diabetes revealed changes in AGP corresponding to alterations in regimen The AGP provides a new approach to the evaluation of glycemic control, with applications to patient and physician education, clinical investigation, and individual patient care

Effect of source of dietary carbohydrate on plasma glucose and insulin responses to mixed meals in subjects with NIDDM.

Abstract: It has been demonstrated that carbohydrate-rich foods result in different plasma glucose responses when eaten alone by normal subjects and patients with non-insulin-dependent diabetes mellitus (NIDDM). This study was designed to test if the glycemic response to mixed meals can be altered by selecting carbohydrate-rich foods based on their glycemic potency. Consequently, three test meals were developed that should have yielded high-, intermediate-, and low-glycemic responses based on the published glycemic index of all the carbohydrate foods in the meals. The test meals were consumed by normal individuals and patients with NIDDM, and the resultant plasma glucose and insulin responses were determined. The results indicated that the plasma glucose responses after the meals did not vary as a function of their glycemic potency in either the normal or NIDDM subjects. There were no significant differences in the plasma insulin responses for either group. These results indicate that the plasma glucose response to mixed meals did not vary as a function of the calculated glycemic potencies. Therefore, the glycemic response to a mixed meal was not predicted on the basis of the published values of the glycemic index of the individual carbohydrate foods included in the meal.

Effect of metformin on insulin-stimulated glucose turnover and insulin binding to receptors in type II diabetes.

Abstract: Euglycemic insulin glucose-clamp and insulin-binding studies on erythrocytes and monocytes were performed in seven type II (non-insulin-dependent) diabetic subjects before and after 4 wk of metformin treatment (850 mg 3 times/day) and in five obese subjects with normal glucose tolerance. Glucose turnover was also measured at basal insulin concentrations and during hyperinsulinemic euglycemic clamps. During euglycemic insulin-glucose clamps, diabetic subjects showed glucose disposal rates of 3.44 +/- 0.42 and 7.34 +/- 0.34 mg X kg-1 X min-1 (means +/- SD) before metformin at insulin infusion rates of 0.80 and 15.37 mU X kg-1 X min-1, respectively. With the same insulin infusion rates, glucose disposal was 4.94 +/- 0.55 (P less than .01) and 8.99 +/- 0.66 (P less than .01), respectively, after metformin treatment. Glucose disposal rates in normal obese subjects were 5.76 +/- 0.63 (P less than .01) and 10.92 +/- 1.11 (P less than .01) at 0.80 and 15.37 mU X kg-1 X min-1, respectively. Insulin maximum binding to erythrocytes in diabetics was 9.6 +/- 4.2 and 5.8 +/- 2.6 X 10(9) cells (means +/- SD) before and after metformin treatment, respectively (NS). Insulin maximum binding to monocytes in diabetics was 6.2 +/- 2.3 X 10(7) cells before and 5.0 +/- 1.6% after metformin. Hepatic glucose production was higher in the diabetic patients at basal insulin levels, but not at higher insulin concentrations, and was not significantly changed by drug treatment. Basal glucose and insulin concentrations decreased with metformin. Thus, metformin treatment improved glucose disposal rate without significant effect on insulin-binding capacity on circulating cells.(ABSTRACT TRUNCATED AT 250 WORDS)

Factors Affecting Staphylococcal Colonization Among NIDDM Outpatients

Abstract: Because colonization with Staphylococcus aureus probably predisposes to staphylococcal infections, we examined several factors that may be associated with staphylococcal carriage in outpatients with non-insulin-dependent diabetes mellitus and in nondiabetic controls. Nose and skin carrier rates for 59 diabetic patients were significantly greater (30.5%) than for 44 controls (11.4%) ( P = .02), but rates did not differ significantly between diabetic patients who injected insulin (31.0%) and those who did not (30.0%). Among the diabetic patients, staphylococcal colonization was not significantly correlated ( P > .05) with recent antibiotic treatment, age, race, or clinical duration of diabetes but was inversely correlated ( P

Reduced albuminuria after dietary protein restriction in insulin-dependent diabetic patients with clinical nephropathy.

Abstract: Recent clinical investigations have demonstrated that an early restriction of dietary protein intake may reduce the rate of progression of chronic renal failure in humans. In this study the effects of a restricted-protein diet on kidney function in type I diabetic patients with clinical nephropathy were evaluated. Sixteen patients (9 men, 7 women) with mean age 37.1 +/- 9.8 yr, mean duration of diabetes 17.7 +/- 6.6 yr, proteinuria greater than 0.5 g/24 h, and serum creatinine concentration of 0.7-1.9 mg/dl were studied. Patients were randomly divided into two groups. The low-protein diet (LPD) group comprised seven patients who were kept for 4.5 +/- 1 mo on a diet containing 0.71 +/- 0.12 g X kg-1 X day-1 protein. The normal-protein diet (NPD) group comprised nine patients as controls maintained for 11.7 +/- 7 mo on their usual diabetic diet containing 1.44 +/- 0.12 g X kg-1 X day-1 protein. All patients were studied every 1-2 mo. Metabolic control was assessed by evaluation of 5-8 blood glucose determinations/day and by glycosylated hemoglobin, whereas renal function was evaluated by albumin, IgG and beta 2-microglobulin urinary excretion rates, serum creatinine concentration, and creatinine clearance. At each visit, serum concentrations of total protein, albumin, phosphate, calcium, and electrolytes and weight and blood pressure were also measured. A significant reduction (434 +/- 244 to 205 +/- 212 micrograms/min, mean +/- SD) in albumin excretion rate was found in all LPD patients after dietary protein restriction, with a significant reincrease (689 +/- 201 micrograms/min) in the same patients several months after interruption of diet.(ABSTRACT TRUNCATED AT 250 WORDS)

Early Loss of Blue-Sensitive Color Vision in Patients With Type I Diabetes

Abstract: Existing methods for early detection of ocular injury from diabetes have serious limitations. We describe a new method, measuring visual flicker discrimination of the blue-sensitive mechanism of vision. This method is noninvasive, quantitative, and capable of distinguishing two types of impairment. Blue-flicker discrimination was measured in 10 adults with type I (insulin-dependent) diabetes for less than 5 yr. Although no evidence of diabetic changes was detected by careful ophthalmic examination by an experienced ophthalmologist, 12 of 19 eyes (63%) had flicker discrimination scores considered abnormal in comparison with those of a control group, and 8 of 10 subjects (80%) had at least 1 eye with abnormal performance. In all but 2 abnormal eyes the deficit of blue-flicker discrimination was of the "absorptive" type, suggesting increased absorbance or scattering of blue light in the optical media. These data show that a functional impairment of vision can be measured very early in the course of type I diabetes, before visible retinopathy is present, and suggest this test procedure may have both investigative and clinical applications.

Primary prevention of diabetes mellitus.

Abstract: Diabetes mellitus is one of the chronic noncommunicable diseases that have increased markedly in this century. The discovery of insulin and other drugs for lowering hyperglycemia have certainly reduced mortality from acute complications of diabetes and improved the quality of life of many diabetic patients. Recent advances in research into the etiology and natural history of diabetes have increased our knowledge about different types of diabetes to such an extent that primary prevention of diabetes mellitus is becoming a reality. Until now, few studies have attempted to test measures for primary prevention of diabetes. Therefore, the data supporting the possibility for primary prevention are largely indirect and need to be tested in preventive trials or in community-based prevention programs. We believe, however, that the time is right to start action in populations in which the prevalence of diabetes is known to have clearly increased recently. We summarize the evidence that can be used as the scientific basis of primary prevention of diabetes mellitus.

Postoperative Management of Diabetes Mellitus: Steady-State Glucose Control With Bedside Algorithm for Insulin Adjustment

Abstract: An algorithm was developed to determine whether an individualized insulin infusion could maintain plasma glucose in a desirable steady state after surgery. In 24 patients, insulin was provided according to a "glucose-feedback" formula to maintain plasma glucose between 120 and 180 mg/dl (6.7-10.0 mM). Initial plasma glucose was elevated, 218 +/- 16 mg/dl (mean +/- SE 12.1 +/- 0.9 mM), but reached the target range after 8 h and remained steady for the rest of the study period. Insulin requirements varied considerably, 0.5-5.0 U/h. Infusion rates were correlated with initial plasma glucose but not with previous insulin dose, HbA1c, or percent ideal body weight. Although insulin needs cannot be predicted, plasma glucose can be maintained in a desirable range after surgery via a simple formula suitable for implementation by general ward nurses.

Glyburide decreases insulin requirement, increases beta-cell response to mixed meal, and does not affect insulin sensitivity: effects of short- and long-term combined treatment in secondary failure to sulfonylurea.

Abstract: In 20 patients with non-insulin-dependent diabetes mellitus (NIDDM) and secondary failure to sulfonylurea, a double-blind randomized study was performed comparing two regimes: insulin plus placebo (IP) and insulin plus glyburide (IG). The protocol included two hospitalization periods (days 1-18 and 78-85) and follow-up at the outpatient clinic for 325 days. The metabolic control was kept as tight as possible. The subjects underwent normoglycemic clamp studies and meal tests with determination of insulin, C-peptide, glucagon, somatostatin, and gastric inhibitory polypeptide in plasma. On IG, they demonstrated marked and long-lasting improvement of metabolic control: HbA1c decreased from 11.1 +/- 0.3% on day 3 to 8.3 +/- 0.4% (P less than .001) on day 78 and 9.1 +/- 0.5% (P less than .001) on day 325. In subjects on IP, the corresponding values were 10.3 +/- 0.5, 8.4 +/- 0.4 (P less than .001), and 8.9 +/- 0.5% (P less than .05). Body weight increased by 6.0 +/- 1.5 kg (P less than .005) on IG and 2.9 +/- 2.1 kg (NS) on IP. The daily insulin requirement decreased on IG from 62.5 +/- 12.9 U/day on day 7 to 33.5 +/- 8.8 U/day on day 83 and 34.6 +/- 8.9 U/day on day 325. On IP the insulin requirement was almost constant: 62.0 +/- 10.7 U/day on day 7, 55.5 +/- 7.7 U/day on day 83, and 54.7 +/- 7.9 U/day on day 325. Insulin sensitivity measured with the hyperinsulinemic clamp (plasma insulin approximately equal to 130 microU/ml) was similar on IP and IG at the initiation of the study and was unchanged on days 18 and 85. A key observation of this study, although the mechanism is unclear, is that isoglycemic-meal-related insulin requirement was diminished by insulin treatment, indicating improvement of meal-related insulin sensitivity. Glyburide increased basal and meal-but not glucagon-stimulated insulin and C-peptide levels, and also augmented the effect of meals on somatostatin release. We conclude that in NIDDM, IG regime promptly and continuously decreased insulin requirement and improved metabolic control. This effect is, at least during the first 3 mo, mainly due to enhanced insulin secretion. IG and IP treatment had no effect on insulin sensitivity during hyperinsulinemic-normoglycemic clamp, whereas meal-related insulin sensitivity was augmented.

Role of metformin in treatment of diabetes mellitus

Abstract: Metformin, a biguanide antidiabetic agent that can be administered either alone or in combination with sulfonylureas, has been extensively used in Europe and Canada. The mechanism of action of metformin and other biguanides is not completely understood, but recent in vitro and in vivo studies suggest that metformin may act in part by both increasing the binding of insulin to its receptor and potentiating insulin action. Metformin, because of its chemical structure, does not interact with the liver and has a short half-life. Consequently, lactic acidosis, which is a rare complication of metformin, has not been associated with the proper use of this drug. In addition to its antidiabetic actions, metformin causes weight loss in obese diabetic patients and may be useful in managing associated lipid disorders.

Proteinuria in newly diagnosed type II diabetic patients.

Abstract: Urinary excretion of albumin, IgG, and beta 2-microglobulin was examined in 132 (69 men, 63 women) newly diagnosed, middle-aged type II diabetic patients and in 144 (62 men, 82 women) nondiabetic control subjects. Both male (N = 57) and female (N = 29) diabetic patients with normal urinary sediment showed an increased excretion of albumin compared with the respective nondiabetic subjects, and male diabetic patients also had an increased IgG excretion. No consistent difference was found in urinary beta 2-microglobulin concentration between the diabetic and nondiabetic subjects. In all, 19.5% of the diabetic subjects with normal urinary sediment (12 men, 5 women) showed urinary albumin concentration exceeding the highest value (35 mg/24 h) found in nondiabetic subjects without renal disease. The urinary excretion of albumin in the diabetic subjects was not associated with the presence of hypertension or coronary heart disease or with the fasting blood glucose or serum insulin levels measured at diagnosis of diabetes. In male diabetic subjects with urinary albumin excretion greater than 35 mg/24 h, a reduced creatinine clearance was found, suggesting the presence of structural damage associated with diabetic nephropathy. The early increase of urinary albumin excretion in type II diabetic patients may be mostly functional in nature. However, some patients may have structural renal damage associated with diabetic nephropathy present at diagnosis.

Factors Affecting Interpretation of Postprandial Glucose and Insulin Areas

Abstract: Recently there has been an increased interest in determining the circulating glucose concentration after the ingestion of various individual foods and mixed meals. The purpose of these determinations is to systematically rank foods with respect to their quantitative effect on postmeal glucose concentration. Potentially such data could be useful in designing a diet for individuals with diabetes. We believe this concept is good. However, several factors that may affect interpretation of the data used to develop this ranking need to be considered before the utility of this approach to dietary management can be assessed: 1) duration of time over which the data are collected and analyzed; 2) use of absolute versus incremental areas in the determinations; 3) inclusion or exclusion of negative areas if incremental areas are used; 4) differences in response to a given food in males compared with females; 5) severity of diabetes; 6) confounding effects of oral agents or insulin treatment; 7) reproducibility of data; 8) differences in collection of blood sample; 9) food composition, processing, and preparation; 10) the dose-response relationship to ingestion of a given carbohydrate; 11) the meal being studied, i.e., first, second, or third meal of the day; and 12) a possible effect of the composition of the previous meal, if the response is tested to any meal other than the first meal of the day.

Remission in IDDM: Prospective Study of Basal C-Peptide and Insulin Dose in 268 Consecutive Patients

Abstract: To elucidate beta-cell function, insulin requirement, and remission period in insulin-dependent diabetes mellitus (IDDM), a study was undertaken comprising 268 patients consecutively admitted to Steno Memorial Hospital with newly diagnosed IDDM. The patients were characterized by sex, age, and seasonal variation at onset of diabetes mellitus. During the first 36 mo of the disease, an evaluation was performed for basal C-peptide, HbA1c, and insulin dose per kilogram. Total remission was interpreted as complete discontinuation of insulin therapy for at least 1 wk while still metabolically well controlled, and partial remission was interpreted as an insulin need that was less than or equal to 50% of the insulin dose at discharge from the hospital. During the first 18 mo of the disease, 12.3% of the patients entered total remission (median 6 mo), and 18.3% of the patients entered partial remission (median 6 mo). Patients entering remission had significantly higher basal C-peptide levels than those who did not. Sex, age, and initial HbA1c levels did not influence the frequency of remission.

Comparison of Intravenous Glucagon and Dextrose in Treatment of Severe Hypoglycemia in an Accident and Emergency Department

Abstract: Hypoglycemia is a serious problem in insulin-treated diabetic patients. In this study the efficacy of intravenous glucagon (1 mg) was compared with that of intravenous dextrose (25 g) in the treatment of hypoglycemia in insulin-treated patients attending an accident and emergency department. In addition, the prevailing glycemic control of these patients was compared with patients routinely attending a diabetic outpatient clinic. Both intravenous glucagon and dextrose were effective in the treatment of hypoglycemic coma. There was a difference in the glycemic profile after intravenous glucagon compared with intravenous dextrose, and recovery of a normal level of consciousness after glucagon was slower than after dextrose (6.5 vs. 4.0 min, respectively; P less than .001), although the average duration of hypoglycemic coma was 1.4 h. The glucagon- and dextrose-treated groups had significantly lower HbA1 than comparable patients routinely attending the clinic (9.5 +/- 0.8 vs. 12.0 +/- 3.8%, respectively; P less than .001). In view of the ease of administration and the small risk of vascular and extravascular complications, intravenous glucagon appears to be a useful alternative to intravenous dextrose in the treatment of severe hypoglycemia.

Comparison of pharmacokinetics, metabolic effects and mechanisms of action of glyburide and glipizide during long-term treatment.

Abstract: Fourteen non-insulin-dependent diabetic (NIDDM) patients continued their previous medication (7 on glyburide, 7 on glipizide) for 6 mo, after which they switched to the alternate treatment for another 6 mo. The treatment periods were followed by 1 mo of placebo. The sulfonylurea dose was increased to achieve fasting plasma glucose levels less than 9 mM or to a total maximum daily dose of 25 mg. The mean final doses of glyburide (14.7 +/- 2.4 mg/day) and glipizide (15.2 +/- 2.2 mg/day) were similar. Postprandial (postdose) glipizide levels were higher than those of glyburide, whereas fasting (predose) glyburide concentrations were higher than those of glipizide. Both treatments improved glucose control by 25% compared with placebo. Glipizide therapy evoked higher postprandial insulin concentrations than did glyburide, whereas basal insulin concentrations were higher during glyburide. Insulin sensitivity, assessed by an insulin tolerance test, was more improved with glyburide than with glipizide. In conclusion, overall glucose control is similarly improved by glyburide and glipizide. However, glipizide amplifies the plasma insulin response to meals more than glyburide, whereas glyburide enhances basal insulin secretion more than glipizide. Both pharmacokinetic and pharmacodynamic factors may contribute to these differences.