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OBJECTIVE Increased glycemic variability has been reported to be associated with the risk of hypoglycemia and possibly diabetes complications and is believed to be due to β-cell dysfunction. However, it [...]

OBJECTIVE Previous studies have demonstrated aberrant glucagon physiology in the setting of type 1 diabetes (T1D) but have not addressed the potential impact of ambient glycemia on this glucagon response. [...]

The Diabetes Control and Complications Trial (DCCT) (1) and its observational follow-up, the Epidemiology of Diabetes Interventions and Complications (EDIC) Study (2), are celebrating the 30th anniversary since the start [...]

OBJECTIVE--Short leg length, a marker of early childhood deprivation, has been used in studies of the association of early life conditions with adult chronic disease risk. The objective of this [...]

OBJECTIVE--People with type 1 diabetes are at high risk of premature atherosclerosis. Existing evidence suggests that impaired vitamin D metabolism may contribute to the development of atherosclerosis. We tested associations [...]

OBJECTIVE--To compare ultra-long-acting insulin degludec with glargine for efficacy and safety in insulin-naive patients with type 2 diabetes inadequately controlled with oral antidiabetic drugs (OADs). RESEARCH DESIGN AND METHODS--In this [...]

Background: The delivery of excess maternal nutrients to the fetus is known to increase the risk of macrosomia, even among infants of women without gestational diabetes mellitus. With the current obesity epidemic, maternal adiposity and its associated effects on circulating adipokines and inflammatory proteins may now have a greater impact on fetal growth. We sought to evaluate the independent effects of maternal glycemia, lipids, obesity, adipokines and inflammation on infant birth weight. Methods: We included 472 women who underwent an oral glucose tolerance test in late pregnancy and were found not to have gestational diabetes; 104 (22.0%) had gestational impaired glucose tolerance. We also measured fasting levels of insulin, low- and high-density lipoprotein cholesterol, triglycerides, leptin, adiponectin and C-reactive protein. Obstetric outcomes were assessed at delivery. Results: The mean birth weight was 3481 g (standard deviation 493 g); 68 of the infants were large for gestational age. On multiple linear regression analysis, positive determinants of birth weight were length of gestation, male infant, weight gain during pregnancy up to the time of the oral glucose tolerance test, body mass index (BMI) before pregnancy and impaired glucose tolerance in pregnancy. Leptin, adiponectin and C-reactive protein levels were each negatively associated with birth weight. On logistic regression analysis, the significant metabolic predictors of having a large-for-gestational-age infant were BMI before pregnancy (odds ratio [OR] 1.16, 95% confidence interval [CI] 1.05-1.27, per 1 kg/[m.sup.2] increase), weight gain during pregnancy up to the time of the oral glucose tolerance test (OR 1.12, 95% CI 1.05-1.19, per 1 kg increase) and leptin level (OR 0.50, 95% CI 0.30-0.82, per 1 standard deviation change). Interpretation: Among women without gestational diabetes, maternal adiposity and leptin levels were the strongest metabolic determinants of having a large-for-gestational-age infant rather than glucose intolerance and lipid levels., In 1952, J0rgen Pedersen proposed that delivery of excess maternal glucose to the fetus may be responsible for the increased risk of macrosomia among infants of women with diabetes during [...]

OBJECTIVE--A common approach to screening for gestational diabetes mellitus (GDM) is the universal testing of all pregnant women with a l-h, 50-g glucose challenge test (GCT), followed by a diagnostic [...]

OBJECTIVE--Gestational diabetes mellitus (GDM) is associated with fetal macrosomia and maternal postpartum dysglycemia, insulin resistance, and 13-cell dysfunction. Indeed, in practice, a prior pregnancy that resulted in a large-for-gestational-age (LGA) [...]

OBJECTIVE--The increased risk of type 2 diabetes in women with glucose intolerance in pregnancy is mediated by deterioration of their [beta]-cell function, which occurs as early as the first year [...]

OBJECTIVE--To examine the prospective associations of baseline vitamin D [25-hydroxyvitamin D; 25(OH)D] with insulin resistance (IR), β-cell function, and glucose homeostasis in subjects at risk for type 2 diabetes. RESEARCH DESIGN AND METHODS--We followed 489 subjects, aged 50 ± 10 years, for 3 years. At baseline and follow-up, 75-g oral glucose tolerance tests (OGTTs) were administered. IR was measured using the Matsuda index ([IS.sub.OGTT]) and the homeostasis model assessment of IR (HOMA-IR), β-cell function was determined using both the insulinogenic index divided by HOMA-IR (IGI/IR) and the insulin secretion sensitivity index-2 (ISSI-2), and glycemia was assessed using the area under the glucose curve ([AUC.sub.glucose]). Regression models were adjusted for age, sex, ethnicity, season, and baseline value of the outcome variable, as well as baseline and change in physical activity, vitamin D supplement use, and BMI. RESULTS--Multivariate linear regression analyses indicated no significant association of baseline 25(OH)D with follow-up [IS.sub.OGTT] or HOMA-IR. There were, however, significant positive associations of baseline 25(OH)D with follow-up IGI/IR (β = 0.005, P = 0.015) and ISSI-2 (β = 0.002, P = 0.023) and a significant inverse association of baseline 25(OH)D with follow-up [AUC.sub.glucose] (β = -0.001, P = 0.007). Progression to dysglycemia (impaired fasting glucose, impaired glucose tolerance, or type 2 diabetes) occurred in 116 subjects. Logistic regression analyses indicated a significant reduced risk of progression with higher baseline 25(OH)D (adjusted odds ratio 0.69 [95% CI 0.53-0.89]), but this association was not significant after additional adjustment for baseline and change in BMI (0.78 [0.59-1.02]). CONCLUSIONS--Higher baseline 25(OH)D independently predicted better β-cell function and lower [AUC.sub.glucose] at follow-up, supporting a potential role for vitamin D in type 2 diabetes etiology. Diabetes 60:2947-2953, 2011, Emerging evidence suggests that vitamin D [25-hydroxyvitamin D; 25(OH)D] may play a role in the etiology of type 2 diabetes (1,2). Vitamin D levels are lower in those with type [...]

OBJECTIVE--Optimal glycemic control slows diabetic retinopathy (DR) development and progression and is the standard of care for type 1 diabetes. However, these glycemic goals are difficult to achieve and sustain [...]

OBJECTIVE--In the Canadian Normoglycemia Outcome Evaluation (CANOE) trial, low-dose rosiglitazone/metformin reduced the risk of diabetes in subjects with impaired glucose tolerance by 66% over a median of 3.9 years. We [...]

OBJECTIVE--ADOPT (A Diabetes Outcome Progression Trial) demonstrated that initial monotherapy with rosiglitazone provided superior durability of glycemic control compared with metformin and glyburide in patients with recently diagnosed type 2 diabetes. Herein, we examine measures of β-cell function and insulin sensitivity from an oral glucose tolerance test (OGTT) over a 4-year period among the three treatments. RESEARCH DESIGN AND METHODS--Recently diagnosed, drug-naive patients with type 2 diabetes (4,360 total) were treated for a median of 4.0 years with rosiglitazone, metformin, or glyburide and were examined with periodic metabolic testing using an OGTT. RESULTS--Measures of β-cell function and insulin sensitivity from an OGTT showed more favorable changes over time with rosiglitazone versus metformin or glyburide. Persistent improvements were seen in those who completed 4 years of monotherapy and marked deterioration of β-cell function in those who failed to maintain adequate glucose control with initial monotherapy. CONCLUSIONS--The favorable combined changes in β-cell function and insulin sensitivity over time with rosiglitazone appear to be responsible for its superior glycemic durability over metformin and glyburide as initial monotherapy in type 2 diabetes. Diabetes 60:1552-1560, 2011, In the UK Prospective Diabetes Study (UKPDS), a progressive decline in β-cell function was the major determinant of loss of glycemic control over time in type 2 diabetes (1). However, [...]

OBJECTIVE -- The objective of this study was to determine the degree to which ramipril and/or rosiglitazone changed β-cell function over time among individuals with impaired fasting glucose (IFG) and/or [...]

OBJECTIVE--C-reactive protein (CRP) is closely associated with obesity and cardiovascular disease in both diabetic and nondiabetic populations. In the short term, commonly prescribed antidiabetic agents have different effects on CRP; [...]

OBJECTIVE--To determine the efficacy and safety of liraglutide (a glucagon-like peptide-1 receptor agonist) when added to metformin and rosiglitazone in type 2 diabetes. RESEARCH DESIGN AND METHODS--This 26-week, double-blind, placebo-controlled, [...]

OBJECTIVE--The purpose of this study was to test the hypothesis that any degree of abnormal glucose homeostasis detected on antepartum screening for gestational diabetes mellitus (GDM) should be associated with [...]

OBJECTIVE--The aim of this study was to investigate associations of adiponectin, leptin, C-reactive protein (CRP), interleukin (IL)-6, and serum amyloid A (SAA), individually or in combinations, with risk of incident [...]

OBJECTIVE--Gestational impaired glucose tolerance (GIGT), defined by a single abnormal value on antepartum 3-h oral glucose tolerance test (OGTT), is a metabolically heterogeneous disorder. Indeed, the antepartum metabolic phenotype of [...]

OBJECTIVE--The purpose of this study was to examine possible factors associated with the increased risk of fractures observed with rosiglitazone in A Diabetes Outcome Progression Trial (ADOPT). RESEARCH DESIGN AND [...]

OBJECTIVE--The Diabetes Control and Complications Trial (Diabetes 44:968-983, 1995) presented statistical models suggesting that subjects with similar A1C levels had a higher risk of retinopathy progression in the conventional treatment group than in the intensive treatment group. That analysis has been cited to support the hypothesis that specific patterns of glucose variation, in particular postprandial hyperglycemia, contribute uniquely to an increased risk of microvascular complications above and beyond that explained by the A1C level. RESEARCH DESIGN AND METHODS--We performed statistical evaluations of these models and additional analyses to assess whether the original analyses were flawed. RESULTS--Statistically, we show that the original results are an artifact of the assumptions of the statistical model used. Additional analyses show that virtually all (96%) of the beneficial effect of intensive versus conventional therapy on progression of retinopathy is explained by the reductions in the mean A1C levels, similarly for other outcomes. Furthermore, subjects within the intensive and conventional treatment groups with similar A1C levels over time have similar risks of retinopathy progression, especially after adjusting for factors in which they differ. CONCLUSIONS--A1C explains virtually all of the difference in risk of complications between the intensive and conventional groups, and a given A1C level has similar effects within the two treatment groups. While other components of hyperglycemia, such as glucose variation, may contribute to the risk of complications, such factors can only explain a small part of the differences in risk between intensive and conventional therapy over time., The Diabetes Control and Complications Trial (DCCT) (1) previously presented epidemiologic analyses of the effect of glycemic exposure, as measured by the updated mean A1C and time in the trial, [...]

The treatment options for type 2 diabetes were for many years limited to sulfonylureas, metformin, and insulin. However, in the last decade or so, a number of new oral and [...]

Background: Exenatide therapy is effective in combination with metformin or sulfonylureas for treating type 2 diabetes. Thiazolidinediones (TZDs) also are commonly used, but the efficacy of exenatide with a TZD has not been reported. Objective: To compare the effects of exenatide versus placebo on glycemic control. Design: Placebo run-in, randomized, double-blind, placebo-controlled trial conducted from May 2004 to August 2005. Setting: 49 sites in Canada, Spain, and the United States. Patients: 233 (exenatide group, n = 121; placebo group, n = 112) patients with type 2 diabetes that was suboptimally controlled with TZD treatment (with or without metformin). Mean ([+ or -] SE) baseline glycated hemoglobin [A.sub.1c] level was 7.9% [+ or -] 0.1%. Interventions: Subcutaneous abdominal injections of 10 [micro]g of exenatide or placebo twice daily, added to a TZD (with or without metformin) for 16 weeks. Measurements: The primary outcome was change from baseline in hemoglobin [A.sub.1c] level. Other outcomes were fasting serum glucose level, body weight, self-monitored blood glucose level, and any adverse events. Results: Exenatide treatment reduced hemoglobin [A.sub.1c] level (mean difference, -0.98% [95% CI, -1.21% to -0.74%]), serum fasting glucose level (mean difference, -1.69 mmol/L [-30.5 mg/dL] [CI, -2.22 to -1.17 mmol/L {-40.0 to -21.1 mg/dL}]), and body weight (mean difference, -1.51 kg [CI, -2.15 to -0.88 kg]). Sixteen percent of patients in the exenatide group and 2% of patients in the placebo group discontinued treatment because of adverse events. In the exenatide group, 40% (n = 48) of patients experienced nausea (mostly mild [n = 21] or moderate [n = 19]), 13% experienced vomiting, and 11% experienced hypoglycemia. In the placebo group, 15% of patients experienced nausea, 1% experienced vomiting, and 7% experienced hypoglycemia. Limitations: Combinations with TZDs and sulfonylureas were not tested. Trial duration was relatively short. Only 71% and 86% of patients in the exenatide and placebo groups, respectively, completed the study. Conclusions: Exenatide therapy improved glycemic control, reduced body weight, and caused gastrointestinal symptoms more than placebo in patients with type 2 diabetes that was suboptimally controlled with TZD therapy.

Type 2 diabetes is now epidemic. In the U.S., there has been a 61% increase in incidence between 1990 and 2001 (1). There are currently 1.5 million new cases per [...]

The Epidemiology of Diabetes Interventions and Complications (EDIC) study, an observational follow-up of the Diabetes Control and Complications Trial (DCCT) type 1 diabetes cohort, measured coronary artery calcification (CAC), an index of atherosclerosis, with computed tomography (CT) in 1,205 EDIC patients at ~7-9 years after the end of the DCCT. We examined the influence of the 6.5 years of prior conventional versus intensive diabetes treatment during the DCCT, as well as the effects of cardiovascular disease risk factors, on CAC. The prevalences of CAC >0 and >200 Agatston units were 31.0 and 8.5%, respectively. Compared with the conventional treatment group, the intensive group had significantly lower geometric mean CAC scores and a lower prevalence of CAC >0 in the primary retinopathy prevention cohort, but not in the secondary intervention cohort, and a lower prevalence of CAC >200 in the combined cohorts. Waist-to-hip ratio, smoking, hypertension, and hypercholesterolemia, before or at the time of CT, were significantly associated with CAC in univariate and multivariate analyses. CAC was associated with mean Hb[A.sub.1c] (A1C) levels before enrollment, during the DCCT, and during the EDIC study. Prior intensive diabetes treatment during the DCCT was associated with less atherosclerosis, largely because of reduced levels of AIC during the DCCT., Patients with type 1 diabetes have a high risk of developing cardiovascular disease (CVD), which in young adulthood can be 10-fold higher than in the general population (1,2). The reasons [...]

The epidemic of type 2 diabetes in the latter part of the 20th and in the early 21st century, and the recognition that achieving specific glycemic goals can substantially reduce [...]

A substantial body of evidence has documented the high prevalence of type 2 diabetes and cardiovascular disease (CVD) among people of South-Asian descent, defined on the basis of ancestral origin [...]

The inflammatory factor C-reactive protein (CRP) and the fibrinolytic variables fibrinogen and plasminogen activator-1 (PAI-1) are associated with long-term cardiovascular morbidity. To determine the contribution of body adiposity (BMI), insulin sensitivity (homeostasis model assessment of insulin resistance [HOMA-IR], and glycemia (Hb[A.sub.1c] [A1C]) to the levels of these inflammatory and fibrinolytic variables in recently diagnosed (≤ 3 years), drug-naive, type 2 diabetic subjects (fasting plasma glucose ≤ 10 mmol/l), we examined a representative subgroup (n = 921) of the U.S. cohort in ADOPT (A Diabetes Outcome Progression Trial). The relationship between levels of CRP, fibrinogen, PAI-1 antigen and PAI-1 activity, and baseline variables including National Cholesterol Education Program Adult Treatment Panel III metabolic syndrome phenotype were explored. All four factors increased significantly with increasing numbers of metabolic syndrome components (P = 0.0136 to P < 0.0001). BMI (P < 0.0001) and HOMA-IR (P < 0.0001) but not A1C (P = 0.65) increased with increasing numbers of metabolic syndrome components. Adjustment of CRP levels for BMI eliminated the association between CRP and the number of metabolic syndrome components, while adjusting for HOMA-IR did not (P = 0.0028). The relationships of PAI-1 antigen and PAI-1 activity with the number of metabolic syndrome components were maintained after adjusting for BMI (P = 0.0002 and P =, Increased levels of the nontraditional cardiovascular disease (CVD) risk factors C-reactive protein (CRP), plasminogen activator-1 (PAI-1), and fibrinogen have been associated with increased CVD in the general population (1-4). Type [...]

OBJECTIVE--Gestational diabetes mellitus (GDM), defined by two abnormal glucose values on a 3-h oral glucose tolerance test (OGTT), is associated with insulin resistance and a low serum concentration of adiponectin. [...]

OBJECTIVE--Excessive secretion of the insulin precursor proinsulin, as manifested by an increased serum proinsulin-to-insulin ratio, has been associated with β-cell dysfunction. In women with gestational diabetes mellitus (GDM), previous studies [...]

Background: Patients with type 2 diabetes who do not achieve glycemic control with oral agent therapy eventually require insulin. Objective: To determine the effect on glycemic control of inhaled insulin alone or added to dual oral therapy (insulin secretagogue and sensitizer) after failure of dual oral therapy. Design: Open-label, randomized, controlled trial. Setting: 48 outpatient centers in the United States and Canada. Patients: 309 patients with type 2 diabetes, no clinically significant respiratory disease, and hemoglobin Ale level of 8% to 11% who were receiving dual oral therapy. Measurements: Primary end point was change in hemoglobin [A.sub.1c] level from baseline to 12 weeks. Secondary outcomes included hemoglobin [A.sub.1c] level less than 8% and less than 7%, hypoglycemia, weight, lipid levels, pulmonary function, insulin antibody binding, and adverse events. Intervention: Inhaled insulin (Exubera; Pfizer Inc. [New York, New York], sanofi-aventis Group [Paris, France], and Nektar Therapeutics [San Carlos, California]), titrated to blood glucose, administered alone (n = 104) or added to dual oral agents (n =103) versus oral therapy alone (n = 99). Results: Reductions in hemoglobin [A.sub.1c] level were greater with inhaled insulin. Adjusted treatment group differences for inhaled insulin plus oral agents and inhaled insulin alone compared with continued oral agent therapy were -1.67 percentage points (95% CI, -1.90 to -1.44 percentage points; P < 0.001) and -1.18 percentage points (CI, -1.41 to -0.95 percentage point; P < 0.001), respectively. Hemoglobin [A.sub.1c] level less than 7% was achieved by 32% (inhaled insulin plus oral agents) and by 1% (oral agent therapy) of patients (adjusted odds ratio, 44.7 [CI, 6.0 to 335.2]). Hypoglycemia, mild weight gain, mild cough, and insulin antibodies were more frequent with inhaled insulin than with oral agent therapy alone. Pulmonary function was similar in all groups. Limitations: This study evaluated only patients with hemoglobin [A.sub.1c] levels of 8% to 11%, did not compare inhaled insulin with other insulins or oral therapy except a dual regimen of secretagogue and sensitizer, and lasted only 12 weeks. Conclusions: Inhaled insulin improved overall glycemic control and hemoglobin [A.sub.1c] level when added to or substituted for dual oral agent therapy with an insulin secretagogue and sensitizer. Consistent with other insulin therapies, hypoglycemia and mild weight gain occurred. Pulmonary function showed no between group differences.

Despite a dramatically increasing burden of type 2 diabetes in Aboriginal Canadian communities (1-5), relatively little information is available regarding the prevalence of, and risk factors for, the complications of [...]

The development and progression of microvascular complications have been extensively documented in a cohort of type 1 diabetic subjects enrolled in the Diabetes Control and Complications Trial (DCCT) and followed in the Epidemiology of Diabetes Interventions and Complications (EDIC) study. We describe the association of genetic variation in the ACE gene in 1,365 DCCT/EDIC subjects with incident persistent microalbuminuria (n = 312) and severe nephropathy (n = 115). We studied three markers (rs1800764, insertion/ deletion, and rs9896208) in the ACE gene that allowed us to capture genetic variation in the common haplotypes occurring at frequencies of >5% in Caucasians. Compared with the more frequent genotype (D/I) for the insertion/deletion polymorphism, in multivariate models, the I/I genotype conferred a lower risk for persistent microalbuminuria (hazard ratio [HR] 0.62 [95% CI 0.43-0.89], P = 0.009) and severe nephropathy (0.56 [0.32-0.96], P = 0.033). Variation at the two other markers, rs1800764 and rs9896208, were also associated with these renal outcomes. In addition, homozygosity for the common haplotype TIC (which corresponded to the T, insertion, and C alleles at the three markers, rs1800764, insertion/deletion, and rs9896208, respectively) versus the CDT/TIC haplotype pair was associated with lower risk for development of persistent microalbuminuria (HR 0.49 [0.32-0.75], P = 0.0009) and severe nephropathy (0.41 [0.22-0.78], P = 0.006). Our findings in the DCCT/EDIC cohort provide strong evidence that genetic variation at the ACE gene is associated with the development of nephropathy in patients with type 1 diabetes., Microvascular and neurologic complications of type 1 diabetes result in significant morbidity and mortality. The Diabetes Control and Complications Trial (DCCT) demonstrated that intensive therapy aimed at reducing glycemic exposure [...]

OBJECTIVE--Diabetic patients with inadequate glycemic control ought to have their management intensified. Failure to do so can be termed 'clinical inertia.' Because data suggest that specialist care results in better [...]

Few epidemiological data exist regarding the correlation of anatomic measures of diabetic retinopathy and nephropathy, especially early in the disease processes. The aim of this study was to examine the association of severity of diabetic retinopathy with histological measures of diabetic nephropathy in normoalbuminuric patients with type 1 diabetes. The study included participants (n = 285) in the Renin-Angiotensin System Study (RASS; a multicenter diabetic nephropathy primary prevention trial) who were aged ≥ 16 years and had 2-20 years of type 1 diabetes with normal baseline renal function measures. Albumin excretion rate (AER), blood pressure, serum creatinine, and glomerular filtration rate (GFR) were measured using standardized protocols. Diabetic retinopathy was determined by masked grading of 30° color stereoscopic fundus photographs of seven standard fields using the Early Treatment Diabetic Retinopathy Study (ETDRS) severity scale. Baseline renal structural parameters, e.g., fraction of the glomerulus occupied by the mesangium or mesangial fractional volume [Vv(Mes/glom)] and glomerular basement membrane width, were assessed by masked electron microscopic morphometric analyses of research percutaneous renal biopsies. No retinopathy was present in 36%, mild nonproliferative diabetic retinopathy in 53%, moderate to severe nonproliferative diabetic retinopathy in 9%, and proliferative diabetic retinopathy in 2% of the cohort. Retinopathy was not related to AER, blood pressure, serum creatinine, or GFR. All renal anatomical end points were associated with increasing severity of diabetic retinopathy, while controlling for other risk factors. These data demonstrate a significant association between diabetic retinopathy and preclinical morphologic changes of diabetic nephropathy in type 1 diabetic patients., Epidemiological studies have shown that diabetic retinopathy and nephropathy are closely associated (1-4). Although diabetic retinopathy appears to be more common than nephropathy (90% of patients with ≥ 20 years [...]

A number of patients with type 2 diabetes are GAD antibody positive. A Diabetes Outcome Progression Trial (ADOPT) is a randomized, double-blind clinical trial in recently diagnosed drug-naive patients with type 2 diabetes that allows for the evaluation of GAD positivity in the context of anthropometric and biochemical characteristics. Of the 4,134 subjects enrolled in ADOPT for whom GAD status was obtained, 174 (4.2%) were GAD positive, with the prevalence of GAD antibodies being similar in North America (4.7%) and Europe (3.7%). Although BMI and age were similar, GAD-positive patients had a lower fasting insulin level, compatible with them being more insulin sensitive. The lower fasting insulin concentration was accompanied by a decreased early insulin response to oral glucose. However, when this insulin response was corrected for the degree of insulin sensitivity, GAD-positive and -negative patients had similar β-cell function. Consistent with the difference in insulin sensitivity, GAD-positive patients had higher HDL cholesterol and lower triglyceride levels. In the GAD-positive individuals, the prevalence of the metabolic syndrome as defined by NCEP ATP III (National Cholesterol Education Program Adult Treatment Panel III) was also lower (74.1 vs. 83.7%, P = 0.0009). These phenotypic differences may underlie a potential difference in the natural history of hyperglycemia and its clinical outcomes., A number of patients with phenotypic type 2 diabetes are GAD antibody positive. These individuals have been referred to as having LADA (latent autoimmune diabetes in adults) or type 1.5 [...]

OBJECTIVE--Rapid-acting insulin analogs (insulin lispro and insulin aspart) have emerged as the meal insulin of choice in both multiple daily insulin injection (MDII) therapy and continuous subcutaneous insulin infusion (CSII) [...]

A limited number of studies have reported associations of markers of liver injury, including elevated concentrations of aspartate aminotransferase (AST) and alanine aminotransferase (ALT), with prospective risk of type 2 diabetes. However, only one study has adjusted for a detailed measure of insulin sensitivity (insulin sensitivity index [[S.sub.i]]), which is important given associations of obesity and [S.sub.i] with nonalcoholic fatty liver disease (NAFLD). Our objective was to investigate the associations of elevated AST and ALT with incident type 2 diabetes among 906 participants in the Insulin Resistance Atherosclerosis Study who were nondiabetic at baseline. [S.sub.i] and acute insulin response (AIR) were measured directly from the frequently sampled intravenous glucose tolerance test among black, Hispanic, and non-Hispanic white participants aged 40-69 years. After 5.2 years, 148 individuals had developed type 2 diabetes. Baseline AST and ALT were positively correlated with fasting insulin (r = 0.22 and r = 0.35, respectively), waist circumference (r = 0.18 and r = 0.34), and fasting glucose (r = 0.13 and r = 0.29) and inversely with [S.sub.i] (r = -0.18 and r = -0.30; all P < 0.0001). In separate logistic regression models adjusting for age, sex, ethnicity, clinical center, and alcohol consumption, participants in the highest quartiles (Q4) of AST and ALT were at significantly increased risk of incident type 2 diabetes compared with those in the lowest three quartiles (Q1-Q3): AST: odds ratio (OR) 1.73 (95% CI 1.17-2.57); ALT: OR 2.32 (1.36-3.75). After further adjustment for smoking, waist circumference, triglyceride, HDL, impaired glucose tolerance, [S.sub.i], and AIR, both AST and ALT remained significantly associated with incident type 2 diabetes: AST, Q4 vs. Q1-Q3: OR 1.98 (1.23-3.17); ALT, Q4 vs. Q1-Q3: OR 2.00 (1.22-3.28). There were no interactions of sex, ethnicity, obesity, impaired glucose tolerance, or [S.sub.i] with AST or ALT in the prediction of type 2 diabetes. When entered into the same model with adjustment for demographic variables, both C-reactive protein and ALT independently predicted type 2 diabetes. In addition, AST and ALT were positively associated with incident type 2 diabetes after excluding former and moderate to heavy drinkers. In conclusion, AST and ALT independently predict type 2 diabetes. Baseline elevations of these markers may reflect NAFLD or related pathologies. Diabetes 53:2623-2632, 2004, Over the past several decades, the prevalence rates of overweight and obesity have reached epidemic levels in the U.S. and other Westernized nations (1-4). This is a development of significant [...]

OBJECTIVE--Coronary artery disease is a significant source of morbidity and mortality in patients with diabetes. Angioplasty has been associated with higher rates of restenosis in patients with diabetes. Numerous studies [...]

OBJECTIVE--Adiponectin is emerging as an important protein in the etiology of obesity and related metabolic disorders. The objectives of this study were to determine cross-sectional and prospective associations of adiponectin [...]

Diabetic retinopathy (DR) and diabetic macular edema (DME) are leading causes of blindness in the working-age population of most developed countries. The increasing number of individuals with diabetes worldwide suggests [...]

The Oji-Cree population of the Sandy Lake region of Ontario, Canada, has the third highest prevalence of type 2 diabetes in the world. Changes in their diet and physical activity over the past half-century, particularly the marked increase in consumption of dietary fats, are felt to be important factors accounting for this epidemic. The aim of the present study was to examine the β-cell response to a 48-h approximately twofold elevation of plasma free fatty acids (FFAs) (induced by Intralipid and heparin infusion) in members of the Sandy Lake Oji-Cree population (n = 12) and to compare the response to that in healthy age-matched nondiabetic Caucasian subjects (n = 16). The insulin secretion rate, insulin sensitivity index ([S.sub.I]), and disposition index ([D.sub.I]) (an index of insulin secretion that takes into account the ambient [S.sub.I]) were assessed in response to a 4-h graded intravenous glucose infusion followed by a 20 mmol/l 2-h hyperglycemic clamp. Total insulin secretory response to the graded glucose infusion did not change after a 48-h FFA elevation versus saline control in Caucasians and increased by ~30% in Oji-Cree individuals (P = 0.04 for difference between the two groups). Infusion of heparin-Intralipid reduced [S.sub.I] by ~40% in both groups (P = 0.002). Although [D.sub.I] was markedly reduced by heparin-Intralipid infusion in Caucasians (by ~40%), it was reduced by only 15% in Oji-Cree individuals (P = 0.03 for difference of response between the two groups). However, [S.sub.I] and [D.sub.I] in the Oji-Cree individuals were already much lower than in Caucasians at baseline, in keeping with the very high risk of type 2 diabetes in this population. It is concluded that Oji-Cree individuals from a community at very high risk for developing type 2 diabetes are not more susceptible to the FFA-induced desensitization of glucose-stimulated insulin secretion than healthy non-Natives and, in fact, appear to be less susceptible. Whether this reflects an inherent resistance to lipotoxicity or an already-present lipotoxic effect in this population will require further study., Type 2 diabetes is characterized by defects in both insulin action and insulin secretion (1,2), with a specific defect in glucose-stimulated insulin secretion (GSIS) early in the evolution of this [...]

OBJECTIVES -- To identify diabetes-related characteristics of individuals at different stages of readiness to change to healthy, low-fat eating. RESEARCH DESIGN AND METHODS -- Stage-based differences in demographic, eating-related, health [...]

OBJECTIVE -- This study compared diabetes Treatment As Usual (TAU) with Pathways To Change (PTC), an intervention developed from the Transtheoretical Model of Change (TTM), to determine whether the PTC [...]

OBJECTIVES -- Experimental and observational studies suggest that vitamin E may reduce the risk of cardiovascular (CV) events and of microvascular complications in people with diabetes, However, data from randomized [...]

OBJECTIVE -- Therapies with metformin, sulfonylureas, or insulin improve glycemic control in the short term but do not prevent progressive islet β-cell failure or long-term deterioration in glycemia. Our goal [...]

OBJECTIVE -- The relationship between parity and risk of diabetes is controversial, and little information is available regarding associations between parity and measures of insulin resistance and β-cell function. The [...]