Insulin resistance and beta-cell dysfunction in newly diagnosed type 2 diabetes: Expression, aggregation and predominance. Verona Newly Diagnosed Type 2 Diabetes Study 10.

AIMS: We investigated quantitative expression, mutual aggregation and relation with hyperglycemia of insulin resistance (IR) and beta-cell dysfunction (BCD) in newly diagnosed type 2 diabetes. METHODS: We assessed IR with euglycemic hyperinsulinemic clamp and BCD with modelled glucose/C-peptide response to oral glucose in 729 mostly drug-naïve patients. We measured glycated hemoglobin, pre-prandial, post-prandial and meal-related excursion of blood glucose. RESULTS: IR was found in 87.8% [95% confidence intervals 85.4-90.2] and BCD in 90.0% [87.8-92.2] of subjects, ranging from mild to moderate or severe. Approximately 20% of subjects had solely one defect: BCD 10.8% [8.6-13.1] or IR 8.6% [6.6-10.7]. Insulin resistance and BCD aggregated in most subjects (79.1% [76.2-82.1]). We arbitrarily set nine possible combinations of mild, moderate or severe IR and mild, moderate or severe BCD, finding that each had a similar frequency (∼10%). In multiple regression analyses parameters of glucose control were related more strongly with BCD than with IR. CONCLUSIONS: In newly-diagnosed type 2 diabetes, IR and BCD are very common with a wide range of expression but no specific pattern of aggregation. Beta-cell dysfunction is likely to play a greater quantitative role than IR in causing/sustaining hyperglycemia in newly-diagnosed type 2 diabetes.

Chronic complications in patients with newly diagnosed type 2 diabetes: prevalence and related metabolic and clinical features: the Verona Newly Diagnosed Type 2 Diabetes Study (VNDS) 9.

INTRODUCTION: We explored the presence of chronic complications in subjects with newly diagnosed type 2 diabetes referred to the Verona Diabetes Clinic. Metabolic (insulin secretion and sensitivity) and clinical features associated with complications were also investigated. RESEARCH DESIGN AND METHODS: The comprehensive assessment of microvascular and macrovascular complications included detailed medical history, resting ECG, ultrasonography of carotid and lower limb arteries, quantitative neurological evaluation, cardiovascular autonomic tests, ophthalmoscopy, kidney function tests. Insulin sensitivity and beta-cell function were assessed by state-of-the-art techniques (insulin clamp and mathematical modeling of glucose/C-peptide curves during oral glucose tolerance test). RESULTS: We examined 806 patients (median age years, two-thirds males), of whom prior clinical cardiovascular disease (CVD) was revealed in 11.2% and preclinical CVD in 7.7%. Somatic neuropathy was found in 21.2% and cardiovascular autonomic neuropathy in 18.6%. Retinopathy was observed in 4.9% (background 4.2%, proliferative 0.7%). Chronic kidney disease (estimated glomerular filtration rate <60 mL/min/1.73 m2) was found in 8.8% and excessive albuminuria in 13.2% (microalbuminuria 11.9%, macroalbuminuria 1.3%).Isolated microvascular disease occurred in 30.8%, isolated macrovascular disease in 9.3%, a combination of both in 9.1%, any complication in 49.2% and no complications in 50.8%.Gender, age, body mass index, smoking, hemoglobin A1c and/or hypertension were independently associated with one or more complications. Insulin resistance and beta-cell dysfunction were associated with macrovascular but not microvascular disease. CONCLUSIONS: Despite a generally earlier diagnosis for an increased awareness of the disease, as many as ~50% of patients with newly diagnosed type 2 diabetes had clinical or preclinical manifestations of microvascular and/or macrovascular disease. Insulin resistance might play an independent role in macrovascular disease. TRIAL REGISTRATION NUMBER: NCT01526720.

Role of Exercise in Vascular Function and Inflammatory Profile in Age-Related Obesity.

In western countries, aging is often accompanied by obesity and age-related obesity is characterized by vascular dysfunction and a low-grade inflammatory profile. Exercise is a nonpharmacological strategy able to decrease the development and incidence of risk factors for several health-threatening diseases. Nonetheless, its long-term effect on vascular function and inflammation in age-related obesity is still unclear. The aim of this study was to investigate the effect of regular, supervised exercise on inflammatory profile and vascular function in age-related obesity. We also hypothesized that vascular function and inflammatory profile would have been correlated in overweight and obese individuals. Thirty normal weight (NW; 70 ± 5 years, 23.9 ± 2.6 BMI) and forty overweight and obese elderly (OW&OB; 69 ± 5 years, 30.1 ± 2.3 BMI) regularly taking part in a structured, supervised exercise program were enrolled in the study and evaluated for vascular function (flow-mediated dilation; FMD) and inflammatory profile (plasma CRP, IL-1ß, IL-1ra, IL-6, IL-8, IL-10, TNF-α, and MCP-1). Although no differences between groups were found concerning performance and the weekly amount of physical activity, the OW&OB group compared with the NW group demonstrated higher systolic and diastolic blood pressure (+10%, p = 0.001; +9%, p = 0.005, respectively); lower FMD% (-36%, p < 0.001) and FMD/shear rate (-40%, p = 0.001); and higher levels of CRP (+33%, p = 0.005), IL-6 (+36%, p = 0.048), MCP-1 (+17%, p = 0.004), and TNF-α (+16%, p = 0.031). No correlations between vascular function and inflammation were found in OW&OB or NW. Although exercising regularly, overweight and obese elderly exhibited poorer vascular function and higher proinflammatory markers compared with the leaner group. These results support the idea that exercise alone cannot counteract the negative effect of adiposity on vascular function and inflammatory profile in elderly individuals and these two processes are not necessarily related.