1,721,047 research outputs found
Metabolic abnormalities underlying the different prediabetic phenotypes in obese adolescents.
OBJECTIVE: The aim of this study was to define the metabolic abnormalities underlying the prediabetic status of isolated impaired fasting glucose (IFG), isolated impaired glucose tolerance (IGT), and combined IFG/IGT in obese youth.RESEARCH DESIGN AND METHODS: We used state-of-the-art techniques (hyperinsulinemic-euglycemic and hyperglycemic clamps), applying a model of glucose-stimulated insulin secretion to the glucose and C-peptide concentration, in 40 normal glucose tolerance (NGT), 17 IFG, 23 IGT, and 11 IFG/IGT obese adolescents. Percent fat (by dual-energy x-ray absorptiometry), age, gender and ethnicity were comparable among groups. RESULTS: Peripheral insulin sensitivity was similar between the IFG and NGT groups. In contrast, the IGT and IFG/IGT groups showed marked reductions in peripheral insulin sensitivity (P < 0.002). Basal hepatic insulin resistance index (basal hepatic glucose production x fasting plasma insulin) was significantly increased in IFG, IGT, and IFG/IGT (P < 0.009) compared with NGT. Glucose sensitivity of first-phase insulin secretion was progressively lower in IFG, IGT, and IFG/IGT compared with NGT. Glucose sensitivity of second-phase secretion showed a statistically significant defect only in the IFG/IGT group. In a multivariate regression analysis, glucose sensitivity of first-phase secretion and basal insulin secretion rate were significant independent predictors of FPG (total r(2) = 25.9%). CONCLUSIONS: IFG, in obese adolescents, is linked primarily to alterations in glucose sensitivity of first-phase insulin secretion and liver insulin sensitivity. The IGT group is affected by a more severe degree of peripheral insulin resistance and reduction in first-phase secretion. IFG/IGT is hallmarked by a profound insulin resistance and by a new additional defect in second-phase insulin secretion
Review article: type 2 diabetes and chronic liver disease in the Verona Diabetes Study
Non-alcoholic liver steatosis is associated with metabolic syndrome and type 2 diabetes. The prevalence of this condition in type 2 diabetes is estimated to be between 28 and 55%. Non-alcoholic liver steatosis is not a benign disease because of its potential progression to liver fibrosis, cirrhosis and cancer. The Verona diabetes study, a population-based observational study, on 7148 type 2 diabetic patients after 5 years of follow-up has reported an increased risk of death from gastrointestinal diseases, particularly from chronic liver cirrhosis. Moreover, in the same population after 10 years of follow-up a higher risk of mortality from liver cancer was observed and this risk increased significantly in obese patients (body mass index >30 kg/m(2)). Of note is that obese diabetic patients suffer an even higher prevalence of non-alcoholic liver steatosis. In conclusion, the Verona diabetes study showed an increased risk of mortality from liver cirrhosis and liver cancer in type 2 diabetic patients. Diverse pathophysiological mechanisms can be responsible, i.e. higher alcohol consumption, hepatitis and others but, considering the high prevalence of nonalcoholic liver steatosis in these patients, it is plausible to hypothesize that non-alcoholic liver steatosis may play a significant role in predisposing the liver of diabetics to chronic diseases
Relationship between soluble CD40 ligand and gamma-glutamyltransferase concentrations in non-drinking, young type 1 diabetic individuals
Aims: To assess the association between circulating levels of soluble CD40 ligand (sCD40L), an emerging cardiovascular risk factor, and γ-glutamyltransferase (GGT) activity concentrations in Type 1 diabetic subjects. Methods: Plasma concentrations of sCD40L and GGT activity, a marker of liver dysfunction, were measured in 54 non-smoking, non-drinking, young Type 1 diabetic patients, who were free of diagnosed cardiovascular disease. Results: When participants were grouped according to tertiles of GGT, plasma sCD40L concentrations steadily increased across GGT tertiles (P = 0.007 for trend). Similarly, plasma sCD40L concentrations were positively correlated with plasma GGT levels in the whole group of participants (r = 0.532; P < 0.0001). In multivariate linear regression analysis, plasma GGT activity levels were positively associated with sCD40L (standardized beta coefficient = 0.342; P = 0.027) independently of age, gender, diabetes duration, glycated haemoglobin, total cholesterol and systolic blood pressure. Further adjustment for the presence of diabetic retinopathy and microalbuminuria did not appreciably attenuate this association. Conclusions: Our findings suggest that there is a strong, graded, relationship between plasma GGT activity and sCD40L concentrations in non-smoking, non-drinking, young Type 1 diabetic individuals. This association appears to be independent of numerous confounding factors. Further studies are required to confirm the reproducibility of these results
Increased prevalence of cardiovascular disease in type 1 diabetic patients with non-alcoholic fatty liver disease.
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Increased prevalence of chronic kidney disease in patients with type 1 diabetes and non-alcoholic fatty liver.
Aims: We determined whether non-alcoholic fatty liver is associated with an increased prevalence of chronic kidney disease in Type 1 diabetes.Methods: We studied 343 patients with Type 1 diabetes, who had no history of excessive alcohol consumption or other secondary causes of chronic liver disease. Non-alcoholic fatty liver was diagnosed by ultrasonography. Chronic kidney disease was defined as presence of either abnormal albuminuria (i.e. urinary albumin ⁄ creatinine ratio ‡ 30 mg⁄ g) or estimated glomerular filtration rate of less than 60 ml min)1 1.73 m)2.Results: Compared with those without steatosis, patients with non-alcoholic fatty liver (n = 182) had significantly lower estimated GFR (83.0 27 vs. 93.3 29 ml min)1 1.73 m)2, P < 0.001) and a greater prevalence of abnormal albuminuria (50.0 vs. 20.5%, P < 0.0001) and chronic kidney disease (54.4 vs. 24.2%, P < 0.0001). Multivariable logistic regression analysis revealed that non-alcoholic fatty liver was associated with an increased risk of either abnormal albuminuria (adjusted odds ratio 2.21, 95% CI 1.2–4.1, P = 0.01) or chronic kidney disease (adjusted odds ratio 1.93, 95% CI 1.1–3.6, P = 0.02), independently of age, gender, smoking status, physical activity, diabetes duration,HbA1c, BMI, systolic blood pressure, plasmalipids and use of anti-hypertensive and lipid-lowering medications.Conclusions: Our findings demonstrate that ultrasound-diagnosed non-alcoholic fatty liver is associated with a higher prevalence of chronic kidney disease in patients
Relation of serum gamma-glutamyltransferase to atherogenic dyslipidemia and glycemic control in type 2 diabetes.
We evaluated possible interactions between BMI and serum γ-glutamyltransferase (GGT) concentration and their effects on the prevalence of poor glycemic control and common omorbidities of diabetes. We assessed whether the association of BMI with poor glycemic control, hypertension, atherogenic dyslipidemia (i.e., high triglycerides and/or low high-density lipoprotein (HDL) cholesterol), hypercholesterolemia, and hyperuricemia differed according to serum GGT concentration in a cohort of 3,633 type 2 diabetic individuals. The associations of BMI with different outcome measures were significant, but the associations varied remarkably by GGT concentration. As GGT concentrationincreased, the association of BMI with atherogenic dyslipidemia and glycemic control strengthened (P = 0.01 and 0.004 for interactions, respectively); in contrast, the association of BMI with hypertension, hypercholesterolemia, and hyperuricemia did not change substantially across GGT quartiles. For example, within the lowest GGT quartile, BMI was not associated with atherogenic dyslipidemia or poor glycemic control, whereas in the highest GGT quartile, the prevalence rates ranged from 62.3 to 74.7% for dyslipidemia and from 75.3 to 83% for poor glycemic control. The results remained unchanged after adjustment for sex, age, alcohol consumption, diabetes duration, and diabetestreatment. In conclusion, our findings show that BMI was associated with atherogenic dyslipidemia and poor glycemiccontrol only when serum GGT activity was in its high-normal range. These findings suggest that obesity itself may not be a sufficient risk factor for atherogenic dyslipidemia or poor glycemic control in people with type 2 diabetes
Depressive symptoms and glycaemic control in adults with type 1 diabetes: an exploratory study on the role of family functioning
Psychological distress and family functioning have a considerable impact on diabetes self-management and glycaemic control in individuals with type 1 diabetes (T1D). However, the influence of both individual and family factors on glycaemic control has not been adequately investigated yet. This study aimed at examining the relationship between perceived family functioning and depressive symptoms with the frequency of capillary self-monitoring of blood glucose (SMBG) and glycaemic control (HbA1c) in a large sample of adults with T1D
Beta-cell function across the spectrum of glucose tolerance in obese youth.
The profile of insulin secretion and the role of proinsulin processing across the spectrum of glucose tolerance in obese youth have not been studied. The aims of this study were to define the role of insulin secretion and proinsulin processing in glucose regulation in obese youth. We performed hyperglycemic clamps to assess insulin secretion, applying a model of glucose-stimulated insulin secretion to the glucose and C-peptide concentration data. Thirty obese youth with normal glucose tolerance (NGT), 22 with impaired glucose tolerance (IGT), and 10 with type 2 diabetes were studied. The three groups had comparable anthropometric measures and insulin sensitivity. The glucose sensitivity of first-phase secretion showed a significant stepwise decline from NGT to IGT and from IGT to type 2 diabetes. The glucose sensitivity of second-phase secretion wassimilar in NGT and IGT subjects yet was significantly lower in subjects with type 2 diabetes. Proinsulin-to-insulin ratios were comparable during first- and secondphase secretion between subjects with NGT and IGT and were significantly increased in type 2 diabetes.Obese youth with IGT have a significant defect in first-phase insulin secretion, while a defect in second-phase secretion and proinsulin processing is specific for type 2 diabetes in this age-group
Metformin is associated with low levels of vitamin B12 with no effect on other vitamin levels. A selective action of metformin
Background and aims: Metformin is frequently used in type 2 diabetes. Long-term treatment is associated with low blood levels of vitamin B12. No studies have evaluated whether metformin affects the blood levels of other vitamins with different mechanisms of intestinal absorption. Thus, the aim of this study was to measure vitamin B12 and other vitamin levels in metformin treated type 2 diabetes patients. Methods and results: In 200 ambulatory patients with type 2 diabetes, vitamins B12, A, B1, B6, B9, C and E were measured. Subjects were divided into those taking and those not taking metformin. Vitamin levels were compared in these two groups. Metformin significantly reduced the levels of vitamin B12 compared to patients not taking the drug (227.1 ± 96.9 vs 325.6 ± 176.8 pmol/L, p < 0.001), without affecting the levels of all other measured vitamins. A deficiency of vitamin B12 was found in 21.1 % of patients. Metformin tripled the risk of vitamin B12 deficiency in the multivariate logistic regression model. Conclusions: To the best of our knowledge, this is the first study that shows a specific effect of metformin in reducing the level of vitamin B12 without affecting other vitamin levels
Variability of body weight, pulse pressure and glycemia strongly predict total mortality in elderly type 2 diabetic patients. The Verona Diabetes Study.
Ageing is characterized by a decreased functional reserve, a concept defined as homeostenosis. We assessed the impact of long-term exposure to the average value (mean) or to the variability (coefficient of variation) of fasting glycaemia, body mass index (BMI) and pulse pressure on total mortality in a cohort of type 2 diabetic patients.Our findings suggest that the variability of fasting glycaemia, body weight and blood pressure (BP) is independently associated with an increased risk of all-cause mortality in older type 2 diabetic patients. Future studies are required to confirm the reproducibility of our findings
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