Showing papers in "Diabetes Care in 2005"

The Metabolic Syndrome: Time for a Critical Appraisal Joint statement from the American Diabetes Association and the European Association for the Study of Diabetes

Abstract: The term "metabolic syndrome" refers to a clustering of specific cardiovascular disease (CVD) risk factors whose underlying pathophysiology is thought to be related to insulin resistance. Since the term is widely used in research and clinical practice, we undertook an extensive review of the literature in relation to the syndrome's definition, underlying pathogenesis, and association with CVD and to the goals and impact of treatment. While there is no question that certain CVD risk factors are prone to cluster, we found that the metabolic syndrome has been imprecisely defined, there is a lack of certainty regarding its pathogenesis, and there is considerable doubt regarding its value as a CVD risk marker. Our analysis indicates that too much critically important information is missing to warrant its designation as a "syndrome." Until much needed research is completed, clinicians should evaluate and treat all CVD risk factors without regard to whether a patient meets the criteria for diagnosis of the "metabolic syndrome."

Diabetic neuropathies: a statement by the American Diabetes Association.

Abstract: The diabetic neuropathies are heterogeneous, affecting different parts of the nervous system that present with diverse clinical manifestations. They may be focal or diffuse. Most common among the neuropathies are chronic sensorimotor distal symmetric polyneuropathy (DPN) and the autonomic neuropathies. DPN is a diagnosis of exclusion. The early recognition and appropriate management of neuropathy in the patient with diabetes is important for a number of reasons. 1 ) Nondiabetic neuropathies may be present in patients with diabetes. 2 ) A number of treatment options exist for symptomatic diabetic neuropathy. 3 ) Up to 50% of DPN may be asymptomatic, and patients are at risk of insensate injury to their feet. As >80% of amputations follow a foot ulcer or injury, early recognition of at-risk individuals, provision of education, and appropriate foot care may result in a reduced incidence of ulceration and consequently amputation. 4 ) Autonomic neuropathy may involve every system in the body. 5 ) Autonomic neuropathy causes substantial morbidity and increased mortality, particularly if cardiovascular autonomic neuropathy (CAN) is present. Treatment should be directed at underlying pathogenesis. Effective symptomatic treatments are available for the manifestations of DPN and autonomic neuropathy. This statement is based on two recent technical reviews (1,2), to which the reader is referred for detailed discussion and relevant references to the literature. An internationally agreed simple definition of DPN for clinical practice is “the presence of symptoms and/or signs of peripheral nerve dysfunction in people with diabetes after the exclusion of other causes” (3). However, the diagnosis cannot be made without a careful clinical examination of the lower limbs, as absence of symptoms should never be assumed to indicate an absence of signs. This definition conveys the important message that not all patients with peripheral nerve dysfunction have a neuropathy caused by diabetes. Confirmation can be established with …

Risks for all-cause mortality, cardiovascular disease, and diabetes associated with the metabolic syndrome: a summary of the evidence.

Abstract: OBJECTIVE —In recent years, several major organizations have endorsed the concept of the metabolic syndrome and developed working definitions for it. How well these definitions predict the risk for adverse events in people with the metabolic syndrome is only now being learned. The purpose of this study was to summarize the estimates of relative risk for all-cause mortality, cardiovascular disease, and diabetes reported from prospective studies in samples from the general population using definitions of the metabolic syndrome developed by the National Cholesterol Education Program (NCEP) and World Health Organization (WHO). RESEARCH DESIGN AND METHODS —The author reviewed prospective studies from July 1998 through August 2004. RESULTS —For studies that used the exact NCEP definition of the metabolic syndrome, random-effects estimates of combined relative risk were 1.27 (95% CI 0.90–1.78) for all-cause mortality, 1.65 (1.38–1.99) for cardiovascular disease, and 2.99 (1.96–4.57) for diabetes. For studies that used the most exact WHO definition of the metabolic syndrome, the fixed-effects estimates of relative risk were 1.37 (1.09–1.74) for all-cause mortality and 1.93 (1.39–2.67) for cardiovascular disease; the fixed-effects estimate was 2.60 (1.55–4.38) for coronary heart disease. CONCLUSIONS —These estimates suggest that the population-attributable fraction for the metabolic syndrome, as it is currently conceived, is ∼6–7% for all-cause mortality, 12–17% for cardiovascular disease, and 30–52% for diabetes. Further research is needed to establish the use of the metabolic syndrome in predicting risk for death, cardiovascular disease, and diabetes in various population subgroups.

Diabetic Nephropathy: Diagnosis, Prevention, and Treatment

Abstract: Diabetic nephropathy is the leading cause of kidney disease in patients starting renal replacement therapy and affects ∼40% of type 1 and type 2 diabetic patients. It increases the risk of death, mainly from cardiovascular causes, and is defined by increased urinary albumin excretion (UAE) in the absence of other renal diseases. Diabetic nephropathy is categorized into stages: microalbuminuria (UAE >20 μg/min and ≤199 μg/min) and macroalbuminuria (UAE ≥200 μg/min). Hyperglycemia, increased blood pressure levels, and genetic predisposition are the main risk factors for the development of diabetic nephropathy. Elevated serum lipids, smoking habits, and the amount and origin of dietary protein also seem to play a role as risk factors. Screening for microalbuminuria should be performed yearly, starting 5 years after diagnosis in type 1 diabetes or earlier in the presence of puberty or poor metabolic control. In patients with type 2 diabetes, screening should be performed at diagnosis and yearly thereafter. Patients with micro- and macroalbuminuria should undergo an evaluation regarding the presence of comorbid associations, especially retinopathy and macrovascular disease. Achieving the best metabolic control (A1c 1.0 g/24 h and increased serum creatinine), using drugs with blockade effect on the renin-angiotensin-aldosterone system, and treating dyslipidemia (LDL cholesterol <100 mg/dl) are effective strategies for preventing the development of microalbuminuria, in delaying the progression to more advanced stages of nephropathy and in reducing cardiovascular mortality in patients with type 1 and type 2 diabetes.

Effects of Exenatide (Exendin-4) on Glycemic Control and Weight Over 30 Weeks in Metformin-Treated Patients With Type 2 Diabetes

Abstract: OBJECTIVE —This study evaluates the ability of the incretin mimetic exenatide (exendin-4) to improve glycemic control in patients with type 2 diabetes failing to achieve glycemic control with maximally effective metformin doses. RESEARCH DESIGN AND METHODS —A triple-blind, placebo-controlled, 30-week study at 82 U.S. sites was performed with 336 randomized patients. In all, 272 patients completed the study. The intent-to-treat population baseline was 53 ± 10 years with BMI of 34.2 ± 5.9 kg/m 2 and HbA 1c of 8.2 ± 1.1%. After 4 weeks of placebo, subjects self-administered 5 μg exenatide or placebo subcutaneously twice daily for 4 weeks followed by 5 or 10 μg exenatide, or placebo subcutaneously twice daily for 26 weeks. All subjects continued metformin therapy. RESULTS —At week 30, HbA 1c changes from baseline ± SE for each group were −0.78 ± 0.10% (10 μg), −0.40 ± 0.11% (5 μg), and +0.08 ± 0.10% (placebo; intent to treat; adjusted P 1c ≤7% ( P P CONCLUSIONS —Exenatide was generally well tolerated and reduced HbA 1c with no weight gain and no increased incidence of hypoglycemia in patients with type 2 diabetes failing to achieve glycemic control with metformin.

Care of Children and Adolescents With Type 1 Diabetes A statement of the American Diabetes Association

Abstract: During recent years, the American Diabetes Association (ADA) has published detailed guidelines and recommendations for the management of diabetes in the form of technical reviews, position statements, and consensus statements. Recommendations regarding children and adolescents have generally been included as only a minor portion of these documents. For example, the most recent ADA position statement on “Standards of Medical Care for Patients With Diabetes Mellitus” (last revised October 2003) included “special considerations” for children and adolescents (1). Other position statements included age-specific recommendations for screening for nephropathy (2) and retinopathy (3) in children with diabetes. In addition, the ADA has published guidelines pertaining to certain aspects of diabetes that apply exclusively to children and adolescents, including care of children with diabetes at school (4) and camp (5) and a consensus statement on type 2 diabetes in children and adolescents (6). The purpose of this document is to provide a single resource on current standards of care pertaining specifically to children and adolescents with type 1 diabetes. It is not meant to be an exhaustive compendium on all aspects of the management of pediatric diabetes. However, relevant references are provided and current works in progress are indicated as such. The information provided is based on evidence from published studies whenever possible and, when not, supported by expert opinion or consensus (7). Several excellent detailed guidelines and chapters on type 1 diabetes in pediatric endocrinology texts exist, including those by the International Society of Pediatric and Adolescent Diabetes (ISPAD) (8), by the Australian Pediatric Endocrine Group (www.chw.edu/au/prof/services/endocrinology/apeg), in Lifshitz’s Pediatric Endocrinology (9–11), and by Plotnick and colleagues (12,13). Children have characteristics and needs that dictate different standards of care. The management of diabetes in children must take the major differences between children of various ages and …

Effects of Exenatide (Exendin-4) on Glycemic Control Over 30 Weeks in Patients With Type 2 Diabetes Treated With Metformin and a Sulfonylurea

Abstract: OBJECTIVE —This study evaluated the effects of exenatide, a novel incretin mimetic, in hyperglycemic patients with type 2 diabetes unable to achieve glycemic control with metformin-sulfonylurea combination therapy. RESEARCH DESIGN AND METHODS —A 30-week, double-blind, placebo-controlled study was performed in 733 subjects (aged 55 ± 10 years, BMI 33.6 ± 5.7 kg/m 2 , A1C 8.5 ± 1.0%; means ± SD) randomized to 5 μg subcutaneous exenatide b.i.d. (arms A and B) or placebo for 4 weeks. Thereafter, arm A remained at 5 μg b.i.d. and arm B escalated to 10 μg b.i.d. Subjects continued taking their dose of metformin and were randomized to either maximally effective (MAX) or minimum recommended (MIN) doses of sulfonylurea. RESULTS —Week 30 A1C changes from baseline (±SE) were −0.8 ± 0.1% (10 μg), −0.6 ± 0.1% (5 μg), and +0.2 ± 0.1% (placebo; adjusted P P P ≤ 0.01 vs. placebo). Mild or moderate nausea was the most frequent adverse event. The incidence of mild/moderate hypoglycemia was 28% (10 μg), 19% (5 μg), and 13% (placebo) and appeared lower with MIN than with MAX sulfonylurea treatment. CONCLUSIONS —Exenatide significantly reduced A1C in patients with type 2 diabetes unable to achieve adequate glycemic control with maximally effective doses of combined metformin-sulfonylurea therapy. This improvement in glycemic control was associated with no weight gain and was generally well tolerated.

Prevalence of the metabolic syndrome defined by the International Diabetes Federation among adults in the U.S.

Abstract: OBJECTIVE —The International Diabetes Federation (IDF) has proposed a new definition of the metabolic syndrome that emphasizes central adiposity as determined by ethnic group–specific thresholds of waist circumference. The objective of this study was to estimate the prevalence of this syndrome using the IDF definition among U.S. adults and to compare it with the prevalence estimated using the definition of the National Cholesterol Education Program (NCEP). RESEARCH DESIGN AND METHODS —A total of 3,601 men and women aged ≥20 years from the National Health and Nutrition Examination Survey 1999–2002 were included in the analyses. RESULTS —Based on the NCEP definition, the unadjusted prevalence of the metabolic syndrome was 34.5 ± 0.9% (percent ± SE) among all participants, 33.7 ± 1.6% among men, and 35.4 ± 1.2% among women. Based on the IDF definition, the unadjusted prevalence of the metabolic syndrome was 39.0 ± 1.1% among all participants, 39.9 ± 1.7% among men, and 38.1 ± 1.2% among women. The IDF definition led to higher estimates of prevalence in all of the demographic groups, especially among Mexican-American men. The two definitions similarly classified ∼93% of the participants as having or not having the metabolic syndrome. CONCLUSIONS —In the U.S., the use of the IDF definition of the metabolic syndrome leads to a higher prevalence estimate of the metabolic syndrome than the estimate based on the NCEP definition.

Assessing psychosocial distress in diabetes: development of the diabetes distress scale.

Abstract: OBJECTIVE —The purpose of this study was to describe the development of the Diabetes Distress Scale (DDS), a new instrument for the assessment of diabetes-related emotional distress, based on four independent patient samples. RESEARCH DESIGN AND METHODS —In consultation with patients and professionals from multiple disciplines, a preliminary scale of 28 items was developed, based a priori on four distress-related domains: emotional burden subscale, physician-related distress subscale, regimen-related distress subscale, and diabetes-related interpersonal distress. The new instrument was included in a larger battery of questionnaires used in diabetes studies at four diverse sites: waiting room at a primary care clinic ( n = 200), waiting room at a diabetes specialty clinic ( n = 179), a diabetes management study program ( n = 167), and an ongoing diabetes management program ( n = 158). RESULTS —Exploratory factor analyses revealed four factors consistent across sites (involving 17 of the 28 items) that matched the critical content domains identified earlier. The correlation between the 28-item and 17-item scales was very high ( r = 0.99). The mean correlation between the 17-item total score (DDS) and the four subscales was high ( r = 0.82), but the pattern of interscale correlations suggested that the subscales, although not totally independent, tapped into relatively different areas of diabetes-related distress. Internal reliability of the DDS and the four subscales was adequate (α > 0.87), and validity coefficients yielded significant linkages with the Center for Epidemiological Studies Depression Scale, meal planning, exercise, and total cholesterol. Insulin users evidenced the highest mean DDS total scores, whereas diet-controlled subjects displayed the lowest scores ( P CONCLUSIONS —The DDS has a consistent, generalizable factor structure and good internal reliability and validity across four different clinical sites. The new instrument may serve as a valuable measure of diabetes-related emotional distress for use in research and clinical practice.

The Metabolic Syndrome and 11-Year Risk of Incident Cardiovascular Disease in the Atherosclerosis Risk in Communities Study

Abstract: OBJECTIVE — To assess the magnitude of the association between the National Cholesterol Education Program’s Third Adult Treatment Panel Report (ATP III) definition of the metabolic syndrome and cardiovascular disease (CVD). RESEARCH DESIGN AND METHODS — Cox regression was used to estimate the relative risk of incident coronary heart disease (CHD) and stroke among 12,089 black and white middle-aged individuals in the Atherosclerosis Risk in Communities (ARIC) study. RESULTS — The metabolic syndrome was present in ∼23% of individuals without diabetes or prevalent CVD at baseline. Over an average of 11 years of follow-up, 879 incident CHD and 216 ischemic stroke events occurred. Among the components of the metabolic syndrome, elevated blood pressure and low levels of HDL cholesterol exhibited the strongest associations with CHD. Men and women with the metabolic syndrome were ∼1.5 and 2 times more likely to develop CHD than control subjects after adjustment for age, smoking, LDL cholesterol, and race/ARIC center (sex interaction P < 0.03). Similar associations were found between the metabolic syndrome and incident ischemic stroke. Comparison of receiver operating characteristic curves indicated that the metabolic syndrome did not materially improve CHD risk prediction beyond the level achieved by the Framingham Risk Score (FRS). CONCLUSIONS — Individuals without diabetes or CVD, but with the metabolic syndrome, were at increased risk for long-term cardiovascular outcomes, although statistical models suggested that most of that risk was accounted for by the FRS. Nevertheless, identification of individuals with the metabolic syndrome may provide opportunities to intervene earlier in the development of shared disease pathways that predispose individuals to both CVD and diabetes.

The Burden of Mortality Attributable to Diabetes: Realistic estimates for the year 2000

Abstract: OBJECTIVE —To estimate the global number of excess deaths due to diabetes in the year 2000. RESEARCH DESIGN AND METHODS —We used a computerized generic formal disease model (DisMod II), used by the World Health Organization to assess disease burden through modeling the relationships between incidence, prevalence, and disease-specific mortality. Baseline input data included population structure, age- and sex-specific estimates of diabetes prevalence, and available published estimates of relative risk of death for people with diabetes compared with people without diabetes. The results were validated with population-based observations and independent estimates of relative risk of death. RESULTS —The excess global mortality attributable to diabetes in the year 2000 was estimated to be 2.9 million deaths, equivalent to 5.2% of all deaths. Excess mortality attributable to diabetes accounted for 2–3% of deaths in poorest countries and over 8% in the U.S., Canada, and the Middle East. In people 35–64 years old, 6–27% of deaths were attributable to diabetes. CONCLUSIONS —These are the first global estimates of mortality attributable to diabetes. Globally, diabetes is likely to be the fifth leading cause of death.

Resistance to Insulin Therapy Among Patients and Providers Results of the cross-national Diabetes Attitudes, Wishes, and Needs (DAWN) study

Abstract: OBJECTIVE - To examine the correlates of patient and provider attitudes toward insulin therapy. RESEARCH DESIGN AND METHODS - Data are from surveys of patients with type 2 diabetes not taking insulin (n = 2,061) and diabetes care providers (nurses = 1,109; physicians = 2,681) in 13 countries in Asia, Australia, Europe, and North America. Multiple regression analysis is used to identify correlates of attitudes toward insulin therapy among patients, physicians, and nurses. RESULTS - Patient and provider attitudes differ significantly across countries, controlling for individual characteristics. Patients rate the clinical efficacy of insulin as low and would blame themselves if they had to start insulin therapy. Self-blame is significantly lower among those who have better diet and exercise adherence and less diabetes-related distress. Patients who are not managing their diabetes well (poor perceived control, more complications, and diabetes-related distress) are significantly more likely to see insulin therapy as potentially beneficial. Most nurses and general practitioners (50-55%) delay insulin therapy until absolutely necessary, but specialists and opinion leaders are less likely to do so. Delay of insulin therapy is significantly less likely when physicians and nurses see their patients as more adherent to medication or appointment regimens, view insulin as more efficacious, and when they are less likely to delay oral diabetes medications. CONCLUSIONS - Patient and provider resistance to insulin therapy is substantial, and for providers it is part of a larger pattern of reluctance to prescribe blood glucose-lowering medication. Interventions to facilitate timely initiation of insulin therapy will need to address factors associated with this resistance.

A Comparison of Lipid and Glycemic Effects of Pioglitazone and Rosiglitazone in Patients With Type 2 Diabetes and Dyslipidemia

Abstract: OBJECTIVE—Published reports suggest that pioglitazone and rosiglitazone have different effects on lipids in patients with type 2 diabetes. However, these previous studies were either retrospective chart reviews or clinical trials not rigorously controlled for concomitant glucose- and lipid-lowering therapies. This study examines the lipid and glycemic effects of pioglitazone and rosiglitazone. RESEARCH DESIGN AND METHODS—We enrolled subjects with a diagnosis of type 2 diabetes (treated with diet alone or oral monotherapy) and dyslipidemia (not treated with any lipid-lowering agents). After a 4-week placebo washout period, subjects randomly assigned to the pioglitazone arm (n = 400) were treated with 30 mg once daily for 12 weeks followed by 45 mg once daily for an additional 12 weeks, whereas subjects randomly assigned to rosiglitazone (n = 402) were treated with 4 mg once daily followed by 4 mg twice daily for the same intervals. RESULTS—Triglyceride levels were reduced by 51.9 ± 7.8 mg/dl with pioglitazone, but were increased by 13.1 ± 7.8 mg/dl with rosiglitazone (P CONCLUSIONS—Pioglitazone and rosiglitazone have significantly different effects on plasma lipids independent of glycemic control or concomitant lipid-lowering or other antihyperglycemic therapy. Pioglitazone compared with rosiglitazone is associated with significant improvements in triglycerides, HDL cholesterol, LDL particle concentration, and LDL particle size.

Increasing Prevalence of Gestational Diabetes Mellitus (GDM) Over Time and by Birth Cohort: Kaiser Permanente of Colorado GDM Screening Program

Abstract: OBJECTIVE —The prevalence of gestational diabetes mellitus (GDM) varies in direct proportion with the prevalence of type 2 diabetes in a given population or ethnic group. Given that the number of people with diabetes worldwide is expected to increase at record levels through 2030, we examined temporal trends in GDM among diverse ethnic groups. RESEARCH DESIGN AND METHODS —Kaiser Permanente of Colorado (KPCO) has used a standard protocol to universally screen for GDM since 1994. This report is based on 36,403 KPCO singleton pregnancies occurring between 1994 and 2002 and examines trends in GDM prevalence among women with diverse ethnic backgrounds. RESULTS —The prevalence of GDM among KPCO members doubled from 1994 to 2002 (2.1–4.1%, P P = 0.006), even after adjusting for prior GDM history. CONCLUSIONS —This study shows that the prevalence of GDM is increasing in a universally screened multiethnic population. The increasing GDM prevalence suggests that the vicious cycle of diabetes in pregnancy initially described among Pima Indians may also be occurring among other U.S. ethnic groups.

Continuous glucose monitoring: roadmap for 21st century diabetes therapy.

Abstract: Continuous glucose monitoring provides maximal information about shifting blood glucose levels throughout the day and facilitates the making of optimal treatment decisions for the diabetic patient. This report discusses continuous glucose monitoring in terms of its purposes, technologies, target populations, accuracy, clinical indications, outcomes, and problems. In this context, the medical literature on continuous glucose monitoring available through the end of 2004 is reviewed. Continuous glucose monitoring provides information about the direction, magnitude, duration, frequency, and causes of fluctuations in blood glucose levels. Compared with conventional intensified glucose monitoring, defined as three to four blood glucose measurements per day, continuous monitoring provides much greater insight into glucose levels throughout the day. Continuous glucose readings that supply trend information can help identify and prevent unwanted periods of hypo- and hyperglycemia. The difference between an intermittent and a continuous monitor for monitoring blood glucose is similar to that between a regular camera and a continuous security camera for monitoring an important situation. A regular camera takes discrete, accurate snapshots; its pictures do not predict the future; it produces a small set of pictures that can all be carefully studied; and effort is required to take each picture. A continuous security camera, on the other hand, takes multiple, poorly focused frames; displays a sequential array of frames whose trend predicts the future; produces too much information for each frame to be studied carefully; and operates automatically after it is turned on. The two types of blood glucose monitors differ in much the same way: 1 ) an intermittent blood glucose monitor measures discrete glucose levels extremely accurately, whereas a continuous monitor provides multiple glucose levels of fair accuracy; 2 ) with an intermittent monitor, current blood glucose levels do not predict future glucose levels, but with a continuous monitor, trends in glucose levels do have …

The Effects of Type 1 Diabetes on Cognitive Performance: A meta-analysis

Abstract: OBJECTIVE —To investigate the exact nature and magnitude of cognitive impairments in patients with type 1 diabetes and the possible association with other disease variables, such as recurrent episodes of hypoglycemia and metabolic control. RESEARCH DESIGN AND METHODS —MedLine and PsycLit search engines were used to identify studies on cognitive performance in patients with type 1 diabetes. Effect sizes (Cohen’s d ), which are the standardized differences between the experimental and the control group, were calculated. In the meta-analysis, a combined d value was calculated, expressing the magnitude of associations across studies. RESULTS —A total of 33 studies were identified that met the inclusion criteria. Compared with nondiabetic control subjects, the type 1 diabetic group demonstrated a significantly lowered performance on the following cognitive domains: intelligence ( d = −0.7), speed of information processing ( d = −0.3), psychomotor efficiency ( d = −0.6), visual ( d = −0.4) and sustained attention ( d = −0.3), cognitive flexibility ( d = −0.5), and visual perception ( d = −0.4). Lowered cognitive performance in diabetic patients appeared to be associated with the presence of microvascular complications but not with the occurrence of severe hypoglycemic episodes or with poor metabolic control. CONCLUSIONS —In patients with type 1 diabetes, cognitive dysfunction is characterized by a slowing of mental speed and a diminished mental flexibility, whereas learning and memory are spared.The magnitude of the cognitive deficits is mild to moderate, but even mild forms of cognitive dysfunction might hamper everyday activities since they can be expected to present problems in more demanding situations.

Concentrations of serum vitamin D and the metabolic syndrome among U.S. adults.

Abstract: Accumulating research suggests that circulating concentrations of vitamin D may be inversely related to the prevalence of diabetes (1,2,3,4), to the concentration of glucose (4,5,6,7,8), and to insulin resistance (4,5,8,9). In addition, vitamin D deficiency may be a risk factor for the metabolic syndrome (8,10), a highly prevalent condition among U.S. adults (11). Much remains to be learned, however, about the relationship between vitamin D status and metabolic syndrome. Because this topic has received scant attention and the available information was derived from a small clinically based sample, we sought to examine the nature and strength of the association between serum concentrations of vitamin D and the metabolic syndrome in a large nationally representative sample of the U.S. population. Between 1988 and 1994, a representative sample of the noninstitutionalized civilian U.S. population, selected using a multistage stratified sampling design, participated in the NHANES III (Third National Health and Nutrition Examination Survey). Survey participants were interviewed and invited for a clinical examination (12,13, …

Moderate alcohol consumption lowers the risk of type 2 diabetes: A meta-analysis of prospective observational studies

Abstract: OBJECTIVE - This meta-analysis was undertaken to obtain insight regarding the shape and strength of the relationship between alcohol consumption and the risk of type 2 diabetes, the effects of adjustment for confounders, and the effect of modification by type 2 diabetes definition, sex, and BMI. RESEARCH DESIGN AND METHODS - The 15 original prospective cohort studies that were included comprise 11,959 incident cases of type 2 diabetes in 369,862 individuals who, on average, were followed for 12 years. RESULTS - After pooling the data, a U-shaped relationship was found. Compared with nonconsumers, the relative risk (RR) for type 2 diabetes in those who consumed ≤6 g/day alcohol was 0.87 (95% CI 0.79-0.95). For the moderate consumption ranges of 6-12, 12-24, and 24-48 g/day, RRs of 0.70 (0.61-0.79), 0.69 (0.58-0.81), and 0.72 (0.62-0.84) were found, respectively. The risk of type 2 diabetes in heavy drinkers (≥48 g/day) was equal to that in nonconsumers (1.04 [0.84-1.29]). In general, nonsignificant trends for larger RR reduction associated with moderate alcohol consumption were observed for women compared with men, for crude compared with multivariate-adjusted analyses, and for studies that used self-reports instead of testing for type 2 diabetes definition. No differences in RR reductions were found between individuals with low or high BMI. CONCLUSIONS - The present evidence from observational studies suggests an ∼30% reduced risk of type 2 diabetes in moderate alcohol consumers, whereas no risk reduction is observed in consumers of ≥48 g/day. © 2005 by the American Diabetes Association.

Effects of oral insulin in relatives of patients with type 1 diabetes: The Diabetes Prevention Trial--Type 1.

Abstract: OBJECTIVE This randomized, double-masked, placebo-controlled clinical trial tested whether oral insulin administration could delay or prevent type 1 diabetes in nondiabetic relatives at risk for diabetes. RESEARCH DESIGN AND METHODS We screened 103,391 first- and second-degree relatives of patients with type 1 diabetes and analyzed 97,273 samples for islet cell antibodies. A total of 3,483 were antibody positive; 2,523 underwent genetic, immunological, and metabolic staging to quantify risk of developing diabetes; 388 had a 5-year risk projection of 26-50%; and 372 (median age 10.25 years) were randomly assigned to oral insulin (7.5 mg/day) or placebo. Oral glucose tolerance tests were performed every 6 months. The median follow-up was 4.3 years, and the primary end point was diagnosis of diabetes. RESULTS Diabetes was diagnosed in 44 oral insulin and 53 placebo subjects. Annualized rate of diabetes was similar in both groups: 6.4% with oral insulin and 8.2% with placebo (hazard ratio 0.764, P = 0.189). In a hypothesis-generating analysis of a subgroup with insulin autoantibody (IAA) levels confirmed (on two occasions) > or =80 nU/ml (n = 263), there was the suggestion of benefit: annualized diabetes rate 6.2% with oral insulin and 10.4% with placebo (0.566, P = 0.015). CONCLUSIONS It is possible to identify individuals at high risk for type 1 diabetes and to enroll them in a large, multisite, randomized, controlled clinical trial. However, oral insulin did not delay or prevent type 1 diabetes. Further studies are needed to explore the potential role of oral insulin in delaying diabetes in relatives similar to those in the subgroup with higher IAA levels.

The Association of Comorbid Depression With Mortality in Patients With Type 2 Diabetes

Abstract: OBJECTIVE—We assessed whether patients with comorbid minor and major depression and type 2 diabetes had a higher mortality rate over a 3-year period compared with patients with diabetes alone. RESEARCH DESIGN AND METHODS—In a large health maintenance organization (HMO), 4,154 patients with type 2 diabetes were surveyed and followed for up to 3 years. Patients initially filled out a written questionnaire, and HMO-automated diagnostic, laboratory, and pharmacy data and Washington State mortality data were collected to assess diabetes complications and deaths. Cox proportional hazards regression models were used to calculate adjusted hazard ratios of death for each group compared with the reference group. RESULTS—There were 275 (8.3%) deaths in 3,303 patients without depression compared with 48 (13.6%) deaths in 354 patients with minor depression and 59 (11.9%) deaths among 497 patients with major depression. A proportional hazards model with adjustment for age, sex, race/ethnicity, and educational attainment found that compared with the nondepressed group, minor depression was associated with a 1.67-fold increase in mortality (P = 0.003), and major depression was associated with a 2.30-fold increase (P CONCLUSIONS—Among patients with diabetes, both minor and major depression are strongly associated with increased mortality. Further research will be necessary to disentangle causal relationships among depression, behavioral risk factors (adherence to medical regimens), diabetes complications, and mortality.

Alpha-glucosidase inhibitors for patients with type 2 diabetes: results from a Cochrane systematic review and meta-analysis.

Abstract: OBJECTIVE —To review the effects of monotherapy with α-glucosidase inhibitors (AGIs) for patients with type 2 diabetes, with respect to mortality, morbidity, glycemic control, insulin levels, plasma lipids, body weight, and side effects. RESEARCH DESIGN AND METHODS —We systematically searched the Cochrane Central register of Controlled Trials, MEDLINE, EMBASE, Current Contents, LILACS, databases of ongoing trials, and reference lists, and we contacted experts and manufacturers. Inclusion criteria were randomized controlled trials of at least 12 weeks’ duration, AGI monotherapy compared with any intervention, and one of the following outcome measures: mortality, morbidity, GHb, blood glucose, lipids, insulin levels, body weight, or side effects. Two independent reviewers assessed all abstracts, extracted all data, and assessed quality. We contacted all authors for data clarification. Continuous data were expressed as weighted mean differences and analyzed with a random-effects model. Possible influences of study characteristics and quality were assessed in sensitivity and meta-regression analyses. RESULTS —Forty-one studies were included in the review (30 acarbose, 7 miglitol, 1 voglibose, and 3 combined), and heterogeneity was limited. We found no evidence for an effect on mortality or morbidity. Compared with placebo, AGIs had a beneficial effect on GHb (acarbose −0.77%; miglitol −0.68%), fasting and postload blood glucose and postload insulin. With acarbose dosages higher than 50 mg t.i.d., the effect on GHb was the same, but the occurrence of side effects increased. Acarbose decreased the BMI by 0.17 kg/m2 (95% CI 0.08–0.26). None of the AGIs had an effect on plasma lipids. Compared with sulfonylurea, AGIs seemed inferior with respect to glycemic control, but they reduced fasting and postload insulin levels. For comparisons with other agents, little data were available. CONCLUSIONS —We found no evidence for an effect on mortality or morbidity. AGIs have clear beneficial effects on glycemic control and postload insulin levels but not on plasma lipids. There is no need for dosages higher than 50 mg acarbose t.i.d.

Initiating insulin therapy in type 2 Diabetes: a comparison of biphasic and basal insulin analogs.

Abstract: OBJECTIVE —Safety and efficacy of biphasic insulin aspart 70/30 (BIAsp 70/30, prebreakfast and presupper) were compared with once-daily insulin glargine in type 2 diabetic subjects inadequately controlled on oral antidiabetic drugs (OADs). RESEARCH DESIGN AND METHODS —This 28-week parallel-group study randomized 233 insulin-naive patients with HbA 1c values ≥8.0% on >1,000 mg/day metformin alone or in combination with other OADs. Metformin was adjusted up to 2,550 mg/day before insulin therapy was initiated with 5–6 units BIAsp 70/30 twice daily or 10–12 units glargine at bedtime and titrated to target blood glucose (80–110 mg/dl) by algorithm-directed titration. RESULTS —A total of 209 subjects completed the study. At study end, the mean HbA 1c value was lower in the BIAsp 70/30 group than in the glargine group (6.91 ± 1.17 vs. 7.41 ± 1.24%, P 1c reduction was greater in the BIAsp 70/30 group than in the glargine group (−2.79 ± 0.11 vs. −2.36 ± 0.11%, respectively; P 1c >8.5% (−3.13 ± 1.63 vs. −2.60 ± 1.50%, respectively; P 1c values than glargine-treated subjects (HbA 1c ≤6.5%: 42 vs. 28%, P 1c P P P CONCLUSIONS —In subjects with type 2 diabetes poorly controlled on OADs, initiating insulin therapy with twice-daily BIAsp 70/30 was more effective in achieving HbA 1c targets than once-daily glargine, especially in subjects with HbA 1c >8.5%.

Impact of intensive lifestyle and metformin therapy on cardiovascular disease risk factors in the diabetes prevention program.

Abstract: Objective The Diabetes Prevention Program demonstrated the ability to delay or prevent type 2 diabetes in participants with impaired glucose tolerance (IGT). Participants with IGT are at high risk for cardiovascular disease (CVD), with a marked increase in the number and severity of CVD risk factors. We prospectively assessed the impact of our interventions on hypertension, dyslipidemia, and CVD events. Research design and methods The study group consisted of 3,234 individuals with IGT randomly assigned to receive intensive lifestyle intervention, metformin, or placebo. Annual assessment of blood pressure, lipids, electrocardiogram, and CVD events was undertaken. Results Hypertension was present in 30% of participants at study entry and then increased in the placebo and metformin groups, although it significantly decreased with intensive lifestyle intervention. Triglyceride levels fell in all treatment groups, but fell significantly more with intensive lifestyle intervention. Total cholesterol and LDL cholesterol levels were similar among treatment groups. Intensive lifestyle intervention significantly increased the HDL cholesterol level and reduced the cumulative incidence of the proatherogenic LDL phenotype B. At 3 years of follow-up, the use for pharmacologic therapy to achieve established goals in the intensive lifestyle group was 27-28% less for hypertension and 25% less for hyperlipidemia compared with placebo and metformin groups. Over an average of 3 years, 89 CVD events from 64 participants were positively adjudicated studywide, with no differences among treatment groups. Conclusions Lifestyle intervention improves CVD risk factor status compared with placebo and metformin therapy. Although no differences in CVD events were noted after 3 years, achieved risk factor modifications suggest that longer intervention may reduce CVD event rates.

Psychological insulin resistance in patients with type 2 diabetes: the scope of the problem.

Abstract: To achieve tight glycemic control in type 2 diabetic patients, it may be advantageous to introduce insulin therapy much earlier in the disease course (1). Unfortunately, many patients are reluctant to begin insulin and may delay starting insulin therapy for significant periods of time (2,3). Recent evidence suggests that more than one-quarter of patients may refuse insulin therapy once it is prescribed (4). Little is actually known about this phenomenon, often termed “psychological insulin resistance” (PIR), how common it may be, or why patients feel this way. Therefore, we developed and distributed a PIR self-report survey to a large multicity sample of patients with type 2 diabetes who were not taking insulin. The survey examined their willingness to take insulin if it was prescribed and to identify perceived attitudinal barriers to insulin therapy. Participants at several 1-day conferences for people with diabetes (Taking Control of Your Diabetes) conducted in San Diego, California; Raleigh, North Carolina; Portland, Oregon; Minneapolis, Minnesota; Philadelphia, Pennsylvania; and Honolulu and Hilo, Hawaii completed an anonymous one-page survey concerning insulin attitudes. At the beginning of each conference, an announcement to all participants explained the study, directed them to the questionnaire in their conference syllabus, and asked them to return completed surveys before the conference’s conclusion. The study was approved by the Committee on Human Research at the University of California, San Francisco. An initial questionnaire item assessed willingness to begin insulin therapy, rated from very willing to not unwilling. Patients also rated on a six-point …

Beneficial Effects of a Dietary Approaches to Stop Hypertension Eating Plan on Features of the Metabolic Syndrome

Abstract: OBJECTIVE —To determine the effects of a Dietary Approaches to Stop Hypertension (DASH) eating plan on metabolic risks in patients with the metabolic syndrome. RESEARCH DESIGN AND METHODS —This was a randomized controlled outpatient trial conducted on 116 patients with the metabolic syndrome. Three diets were prescribed for 6 months: a control diet, a weight-reducing diet emphasizing healthy food choices, and the DASH diet with reduced calories and increased consumption of fruit, vegetables, low-fat dairy, and whole grains and lower in saturated fat, total fat, and cholesterol and restricted to 2,400 mg Na. The main outcome measures were the components of the metabolic syndrome. RESULTS —Relative to the control diet, the DASH diet resulted in higher HDL cholesterol (7 and 10 mg/dl), lower triglycerides (−18 and −14 mg/dl), systolic blood pressure (SBP) (−12 and −11 mmHg), diastolic blood pressure (−6 and −7 mmHg), weight (−16 and −14 kg), fasting blood glucose (FBG) (−15 and −8 mg/dl), and weight (−16 and −15 kg), among men and women, respectively (all P P P CONCLUSIONS —The DASH diet can likely reduce most of the metabolic risks in both men and women; the related mechanisms need further study.

Depression and all-cause and coronary heart disease mortality among adults with and without diabetes.

Abstract: OBJECTIVE —The aim of this study was to evaluate the effect of depression on all-cause and coronary heart disease (CHD) mortality among adults with and without diabetes. RESEARCH DESIGN AND METHODS —We studied 10,025 participants in the population-based National Health and Nutrition Examination Survey I Epidemiologic Follow-up Study who were alive and interviewed in 1982 and had complete data for the Center for Epidemiologic Studies Depression Scale. Four groups were created based on diabetes and depression status in 1982: 1 ) no diabetes, no depression (reference group); 2 ) no diabetes, depression present; 3 ) diabetes present, no depression; and i4) diabetes present, depression present. Cox proportional hazards regression models were used to calculate multivariate-adjusted hazard ratios (HRs) of death for each group compared with the reference group. RESULTS —Over 8 years (83,624 person-years of follow-up), 1,925 deaths were documented, including 522 deaths from CHD. Mortality rate per 1,000 person-years of follow-up was highest in the group with both diabetes and depression. Compared with the reference group, HRs for all-cause mortality were no diabetes, depression present, 1.20 (95% CI 1.03–1.40); diabetes present, no depression 1.88 (1.55–2.27); and diabetes present, depression present, 2.50 (2.04–3.08). HRs for CHD mortality were no diabetes, depression present, 1.29 (0.96–1.74); diabetes present, no depression 2.26 (1.60–3.21); and diabetes present, depression present, 2.43 (1.66–3.56). CONCLUSIONS —The coexistence of diabetes and depression is associated with a significantly increased risk of death from all causes, beyond that due to having either diabetes or depression alone.

Dietary Calcium, Vitamin D, and the Prevalence of Metabolic Syndrome in Middle-Aged and Older U.S. Women

Abstract: OBJECTIVE —To examine whether and to what extent intakes of calcium and vitamin D are related to the metabolic syndrome in middle-aged or older women. RESEARCH DESIGN AND METHODS —We analyzed data from 10,066 women aged ≥45 years participating in the Women’s Health Study who were free of cardiovascular disease, cancer, or diabetes and who never used postmenopausal hormones. We used multiple logistic regression models to estimate multivariable odds ratios (ORs) and 95% CIs comparing different dietary intake levels of calcium and vitamin D. RESULTS —In age- and calorie-adjusted analyses, higher intakes of total, dietary, and supplemental calcium were significantly and inversely associated with the prevalence of metabolic syndrome. After further adjusting for smoking status, exercise, alcohol intake, multivitamin use, and parental history of myocardial infarction before age 60 years, the ORs of having the metabolic syndrome for increasing quintiles of total calcium intake were 1.00 (reference), 0.82 (95% CI 0.70–0.97), 0.84 (0.71–0.99), 0.70 (0.59–0.83), and 0.64 (0.54–0.77) ( P for trend P for trend = 0.13) nor supplemental ( P for trend = 0.45) vitamin D was significantly associated with metabolic syndrome. Dietary vitamin D was inversely associated with prevalence of metabolic syndrome but was not independent of total calcium intake. Similar strong relations between intakes of dairy products and metabolic syndrome were also observed. After adjustment for lifestyle and dietary factors, the multivariable ORs comparing highest with lowest intake categories were 0.66 (0.55–0.80) ( P for trend P for trend = 0.05) for total milk intake. CONCLUSIONS —Our results indicate that intakes of calcium and dairy products may be associated with lower prevalence of the metabolic syndrome in middle-aged and older women.

A Comparison of Lipid and Glycemic Effects of Pioglitazone and Rosiglitazone in Patients With Type 2 Diabetes and Dyslipidemia: Response to Bell and Brunzell

Abstract: In his commentary, Bell (1) presents specific criticisms of the head-to-head trial comparing the effects of rosiglitazone with pioglitazone on lipids and lipoproteins. Bell raises a concern over study recruitment (in particular the high rate of screen failures), the exclusion of patients on statin therapy, and the limited data supporting the role of hypertriglyceridemia in cardiovascular risk. By excluding patients on other glucose- and lipid-lowering medication, we were able to demonstrate that the two agents have different effects on each of the components of the lipid profile. In doing so, the differences observed could only be attributed to the active thiazolidinedione (TZD) therapy. Targets for LDL cholesterol were lowered during the active …

Identifying Individuals at High Risk for Diabetes The Atherosclerosis Risk in Communities study

Abstract: Objective To develop and evaluate clinical rules to predict risk for diabetes in middle-aged adults. Research design and methods The Atherosclerosis Risk in Communities is a cohort study conducted from 1987-1989 to 1996-1998. We studied 7,915 participants 45-64 years of age, free of diabetes at baseline, and ascertained 1,292 incident cases of diabetes by clinical diagnosis or oral glucose tolerance testing. Results We derived risk functions to predict diabetes using logistic regression in a random half of the sample. Rules based on these risk functions were evaluated in the other half. A risk function based on waist, height, hypertension, blood pressure, family history of diabetes, ethnicity, and age was performed similarly to one based on fasting glucose (area under the receiver-operating characteristic curve [AUC] 0.71 and 0.74, respectively; P = 0.2). Risk functions composed of the clinical variables plus fasting glucose (AUC 0.78) and additionally including triglycerides and HDL cholesterol (AUC 0.80) performed better (P Conclusions Rules derived from clinical information, alone or combined with simple laboratory measures, can characterize degrees of diabetes risk in middle-aged adults, permitting preventive actions of appropriate intensity. Rules based on the metabolic syndrome are reasonable alternatives to rules derived from risk functions.