Effect of 6-month supervised exercise on low-density lipoprotein apolipoprotein B kinetics in patients with type 2 diabetes mellitus

Although low-density lipoprotein (LDL) cholesterol is often normal in patients with type 2 diabetes mellitus, there is evidence for a reduced fractional catabolic rate and consequently an increased mean residence time (MRT), which can increase atherogenic risk. The dyslipidemia and insulin resistance of type 2 diabetes mellitus can be improved by aerobic exercise, but effects on LDL kinetics are unknown. The effect of 6-month supervised exercise on LDL apolipoprotein B kinetics was studied in a group of 17 patients with type 2 diabetes mellitus (mean age, 56.8 years; range, 38-68 years). Patients were randomized into a supervised group, who had a weekly training session, and an unsupervised group. LDL kinetics were measured with an infusion of 1-(13)C leucine at baseline in all groups and after 6 months of exercise in the patients. Eight body mass index-matched nondiabetic controls (mean age, 50.3 years; range, 40-67 years) were also studied at baseline only. At baseline, LDL MRT was significantly longer in the diabetic patients, whereas LDL production rate and fractional clearance rates were significantly lower than in controls. Percentage of glycated hemoglobin A(1c), body mass index, insulin sensitivity measured by the homeostasis model assessment, and very low-density lipoprotein triglyceride decreased (P < .02) in the supervised group, with no change in the unsupervised group. After 6 months, LDL cholesterol did not change in either the supervised or unsupervised group; but there was a significant change in LDL MRT between groups (P < .05) that correlated positively with very low-density lipoprotein triglyceride (r = 0.51, P < .04) and negatively with maximal oxygen uptake, a measure of fitness (r = -0.51, P = .035), in all patients. The LDL production and clearance rates did not change in either group. This study suggests that a supervised exercise program can reduce deleterious changes in LDL MRT.

Self-monitoring of blood glucose in non-insulin treated patients with type 2 diabetes: a systematic review and meta-analysis

To assess the effect of self-monitoring of blood glucose (SMBG) on glycaemic control in non-insulin treated patients with type 2 diabetes by means of a systematic review and meta-analysis.

Fructose overconsumption causes dyslipidemia and ectopic lipid deposition in healthy subjects with and without a family history of type 2 diabetes

BACKGROUND: Both nutritional and genetic factors are involved in the pathogenesis of nonalcoholic fatty liver disease and insulin resistance. OBJECTIVE: The aim was to assess the effects of fructose, a potent stimulator of hepatic de novo lipogenesis, on intrahepatocellular lipids (IHCLs) and insulin sensitivity in healthy offspring of patients with type 2 diabetes (OffT2D)--a subgroup of individuals prone to metabolic disorders. DESIGN: Sixteen male OffT2D and 8 control subjects were studied in a crossover design after either a 7-d isocaloric diet or a hypercaloric high-fructose diet (3.5 g x kg FFM(-1) x d(-1), +35% energy intake). Hepatic and whole-body insulin sensitivity were assessed with a 2-step hyperinsulinemic euglycemic clamp (0.3 and 1.0 mU x kg(-1) x min(-1)), together with 6,6-[2H2]glucose. IHCLs and intramyocellular lipids (IMCLs) were measured by 1H-magnetic resonance spectroscopy. RESULTS: The OffT2D group had significantly (P < 0.05) higher IHCLs (+94%), total triacylglycerols (+35%), and lower whole-body insulin sensitivity (-27%) than did the control group. The high-fructose diet significantly increased IHCLs (control: +76%; OffT2D: +79%), IMCLs (control: +47%; OffT2D: +24%), VLDL-triacylglycerols (control: +51%; OffT2D: +110%), and fasting hepatic glucose output (control: +4%; OffT2D: +5%). Furthermore, the effects of fructose on VLDL-triacylglycerols were higher in the OffT2D group (group x diet interaction: P < 0.05). CONCLUSIONS: A 7-d high-fructose diet increased ectopic lipid deposition in liver and muscle and fasting VLDL-triacylglycerols and decreased hepatic insulin sensitivity. Fructose-induced alterations in VLDL-triacylglycerols appeared to be of greater magnitude in the OffT2D group, which suggests that these individuals may be more prone to developing dyslipidemia when challenged by high fructose intakes. This trial was registered at clinicaltrials.gov as NCT00523562.

Liraglutide once a day versus exenatide twice a day for type 2 diabetes: a 26-week randomised, parallel-group, multinational, open-label trial (LEAD-6)

BACKGROUND: Unlike most antihyperglycaemic drugs, glucagon-like peptide-1 (GLP-1) receptor agonists have a glucose-dependent action and promote weight loss. We compared the efficacy and safety of liraglutide, a human GLP-1 analogue, with exenatide, an exendin-based GLP-1 receptor agonist. METHODS: Adults with inadequately controlled type 2 diabetes on maximally tolerated doses of metformin, sulphonylurea, or both, were stratified by previous oral antidiabetic therapy and randomly assigned to receive additional liraglutide 1.8 mg once a day (n=233) or exenatide 10 microg twice a day (n=231) in a 26-week open-label, parallel-group, multinational (15 countries) study. The primary outcome was change in glycosylated haemoglobin (HbA(1c)). Efficacy analyses were by intention to treat. The trial is registered with ClinicalTrials.gov, number NCT00518882. FINDINGS: Mean baseline HbA(1c) for the study population was 8.2%. Liraglutide reduced mean HbA(1c) significantly more than did exenatide (-1.12% [SE 0.08] vs -0.79% [0.08]; estimated treatment difference -0.33; 95% CI -0.47 to -0.18; p<0.0001) and more patients achieved a HbA(1c) value of less than 7% (54%vs 43%, respectively; odds ratio 2.02; 95% CI 1.31 to 3.11; p=0.0015). Liraglutide reduced mean fasting plasma glucose more than did exenatide (-1.61 mmol/L [SE 0.20] vs -0.60 mmol/L [0.20]; estimated treatment difference -1.01 mmol/L; 95% CI -1.37 to -0.65; p<0.0001) but postprandial glucose control was less effective after breakfast and dinner. Both drugs promoted similar weight losses (liraglutide -3.24 kg vs exenatide -2.87 kg). Both drugs were well tolerated, but nausea was less persistent (estimated treatment rate ratio 0.448, p<0.0001) and minor hypoglycaemia less frequent with liraglutide than with exenatide (1.93 vs 2.60 events per patient per year; rate ratio 0.55; 95% CI 0.34 to 0.88; p=0.0131; 25.5%vs 33.6% had minor hypoglycaemia). Two patients taking both exenatide and a sulphonylurea had a major hypoglycaemic episode. INTERPRETATION: Liraglutide once a day provided significantly greater improvements in glycaemic control than did exenatide twice a day, and was generally better tolerated. The results suggest that liraglutide might be a treatment option for type 2 diabetes, especially when weight loss and risk of hypoglycaemia are major considerations.

Angiotensin I-converting enzyme-gene-polymorphism: relationship to albumin excretion and blood pressure in pediatric patients with type-I-diabetes mellitus

The purpose of this study was the evaluation of a predictive genetic marker for nephropathy and hypertension in patients with type-I-diabetes mellitus (IDDM). The study was performed on 247 pediatric patients with IDDM. The mean age was 15.5 years (range 3.1-29.3), the mean duration of diabetes was 7.6 years (range 0.1-25.7). Age-related blood pressure and nocturnal albumin excretion rate were compared with the insertion/deletion-(I/D) polymorphism of the angiotensin-I converting enzyme gene. The genotype distribution did not differ significantly between IDDM patients (ID 48%, D 28%, I 24%) and the control group (ID 44%, D 37%, I 19%). Neither in the entire group, nor in patients with IDDM for more than 5 years, was a correlation found bet-ween allele distribution and albumin excretion rate. No correlation was found between genotype and blood pressure. When patients with a chronological age above 12 years were analysed separately, the genotype distribution between the groups with normal and elevated blood pressure showed no significant difference. The previously reported association of the I/D-polymorphism with nephropathy could not be confirmed in this study. The development of microalbuminuria, nephropathy and hypertension will be followed in our pediatric patients.

Insulin increases serum leptin concentrations in children and adolescents with newly diagnosed type I diabetes mellitus with and without ketoacidosis.

AIMS/HYPOTHESIS The aims of this study were to analyse the changes of serum leptin in newly diagnosed children and adolescents with Type I (insulin-dependent) diabetes mellitus after insulin treatment and to examine the possible impact of ketoacidosis on these changes. METHODS Baseline serum leptin concentrations were measured in 28 newly diagnosed Type I diabetic patients [age 8.75 +/- 4.05 years (means +/- SD); BMI 15.79 +/- 2.47 kg/m(2); HbA(1 c) 11.3 +/- 1.9 %] with (n = 18) and without (n = 10) ketoacidosis before commencement of insulin treatment, at the time of diagnosis. Thereafter, during a 4-day course of continuous intravenous insulin injection to gain and maintain euglycaemia, serum leptin concentrations were assessed. RESULTS Baseline serum leptin concentrations, adjusted to age, BMI, sex and pubertal stage, differed among these patients. There was, however, an increase of leptin in all subjects from 1.37 +/- 0.56 ng/ml (mean +/- SD) up to 2.97 +/- 1.52 ng/ml by 117 % (p < 0.0001) after insulin therapy. On average, peak serum leptin concentration was obtained after 42 h of insulin treatment. Further, there was no difference in the mean increase of serum leptin concentrations in the two groups, namely with and without ketoadicosis, of insulin-dependent diabetic children and adolescents. In addition, there was no correlation between serum leptin concentrations and correction of ketoacidosis during insulin treatment. CONCLUSIONS/INTERPRETATION Insulin increases serum leptin, within 1 day, in children and adolescents with newly diagnosed Type I diabetes. Ketoacidosis does not influence this interaction between insulin and leptin.

Exploring the role of viral infection in type 2 diabetes

Viral infection is known to play a role in type I diabetes, but there is a paucity of information on the role of viruses in type 2 diabetes. This research examined the seroprevalence of selected viruses in a group of predominantly Mexican-American patients with End Stage Renal Disease (ESRD). Using a case control design, patients with type 2 diabetes were compared with a group of non-diabetic controls. ^ One hundred and thirteen patients, 83 with type 2 diabetes and 30 controls without diabetes, underwent hemodialysis at the same chronic dialysis facility in San Antonio, Texas. AD subjects were tested for IgG, IgM, and neutralizing antibodies against Coxsackie B viruses (CBV), and IgG and IgM antibodies against cytomegalovirus (CMV) and parvovirus B19 (PVB19). Hepatitis B virus antigen (HBVAg), Hepatitis B virus antibody (HBVAb), Hepatitis C virus antibody (HCVAb), and Rubella (IgG) were also measured. A subset of 91 patients, 66 with diabetes and 25 controls, were tested bimonthly for six months. There was a significant difference (P = 0.04) in the seroprevalence of IgG antibodies to CMV between patients with type 2 diabetes (98%) and non-diabetic controls (87%) in the initial sample (OR = 6.2, 95% CI:1.1–36.0). A greater seroprevalence of CMV IgG antibodies was observed over the six month period among patients with type 2 diabetes (M) compared to controls (84%). This difference was also statistically (P < 0.03), with a greater odds ratio (OR = 12.4, 95% CI: 1.3–116.9), but with larger confidence interval related to the small number of subjects. However, when adjusted for age by logistic regression analysis there was no difference between the groups (OR = 1). ^ After one sample, there was a greater seroprevalence of HCVAb in the group without diabetes (28%), compared to those with type 2 diabetes (10%) (P = 0.04). This difference was no longer significant when adjusted for patient age. The prevalence of antibodies to PVB19, HBSAg, HBV, and Rubella was not significantly different in patients with type 2 diabetes and controls. There were significantly more vascular complications (P < 0.02) among patients with diabetes. ^ These results indicate that the significant associations observed in this population between viral infection with CMV, HCV, and type 2 diabetes are confounded by age. Accelerated atherosclerosis has been associated with age, diabetes, as well as CMV. Latent infection may be a factor that links these processes. ^

Prevalence of type 2 diabetes is higher in peripheral artery disease than in coronary artery disease patients.

Type 2 diabetes mellitus and pre-diabetes are risk factors for atherosclerosis and are highly prevalent in patients with coronary artery disease. However, the prevalence of impaired glucose metabolism in patients with peripheral artery disease is not as well elucidated. We aimed at comparing prevalence rates of type 2 diabetes mellitus and pre-diabetes, which were diagnosed according to the current American Diabetes Association criteria, among 364 patients with peripheral artery disease, 529 patients with coronary artery disease and 383 controls. The prevalence of type 2 diabetes mellitus in peripheral artery disease patients was 49.7%. It was significantly higher in these patients than in coronary artery disease patients (34.4%; p < 0.001) and controls (21.4%; p < 0.001). Adjusted for sex, age and body mass index, odds ratios for type 2 diabetes mellitus were 2.0 (95% confidence interval 1.5-2.6) comparing the peripheral artery disease group with the coronary artery disease group (p < 0.001) and 4.0 (2.8-5.8) comparing the peripheral artery disease group with controls (p < 0.001). The prevalence of pre-diabetes among non-diabetic subjects was high in all three study groups (64.5% in peripheral artery disease patients, 63.4% in coronary artery disease patients and 61.8% in controls), without significant between-group differences. In conclusion, the prevalence of type 2 diabetes mellitus is even higher in peripheral artery disease patients than in coronary artery disease patients. This observation underlines the need to consider impaired glucose regulation in the management of peripheral artery disease.

Incidence of and risk factors for severe hypoglycaemia in treated type 2 diabetes mellitus patients in the UK - a nested case-control analysis

AIMS To assess incidence rates (IRs) of and identify risk factors for incident severe hypoglycaemia in patients with type 2 diabetes newly treated with antidiabetic drugs. METHODS Using the UK-based General Practice Research Database, we performed a retrospective cohort study between 1994 and 2011 and a nested case-control analysis. Ten controls from the population at risk were matched to each case with a recorded severe hypoglycaemia during follow-up on general practice, years of history in the database and calendar time. Using multivariate conditional logistic regression analyses, we adjusted for potential confounders. RESULTS Of 130,761 patients with newly treated type 2 diabetes (mean age 61.7 ± 13.0 years), 690 (0.5%) had an incident episode of severe hypoglycaemia recorded [estimated IR 11.97 (95% confidence interval, CI, 11.11-12.90) per 10,000 person-years (PYs)]. The IR was markedly higher in insulin users [49.64 (95% CI, 44.08-55.89) per 10,000 PYs] than in patients not using insulin [8.03 (95% CI, 7.30-8.84) per 10,000 PYs]. Based on results of the nested case-control analysis increasing age [≥ 75 vs. 20-59 years; adjusted odds ratio (OR), 2.27; 95% CI, 1.65-3.12], cognitive impairment/dementia (adjusted OR, 2.00; 95% CI, 1.37-2.91), renal failure (adjusted OR, 1.34; 95% CI, 1.04-1.71), current use of sulphonylureas (adjusted OR, 4.45; 95% CI, 3.53-5.60) and current insulin use (adjusted OR, 11.83; 95% CI, 9.00-15.54) were all associated with an increased risk of severe hypoglycaemia. CONCLUSIONS Severe hypoglycaemia was recorded in 12 cases per 10,000 PYs. Risk factors for severe hypoglycaemia included increasing age, renal failure, cognitive impairment/dementia, and current use of insulin or sulphonylureas.

Poorly controlled type 2 diabetes mellitus is associated with a decreased risk of incident gout: a population-based case-control study

OBJECTIVE The aim of this study was to explore the risk of incident gout in patients with type 2 diabetes mellitus (T2DM) in association with diabetes duration, diabetes severity and antidiabetic drug treatment. METHODS We conducted a case-control study in patients with T2DM using the UK-based Clinical Practice Research Datalink (CPRD). We identified case patients aged ≥18 years with an incident diagnosis of gout between 1990 and 2012. We matched to each case patient one gout-free control patient. We used conditional logistic regression analysis to calculate adjusted ORs (adj. ORs) with 95% CIs and adjusted our analyses for important potential confounders. RESULTS The study encompassed 7536 T2DM cases with a first-time diagnosis of gout. Compared to a diabetes duration <1 year, prolonged diabetes duration (1-3, 3-6, 7-9 and ≥10 years) was associated with decreased adj. ORs of 0.91 (95% CI 0.79 to 1.04), 0.76 (95% CI 0.67 to 0.86), 0.70 (95% CI 0.61 to 0.86), and 0.58 (95% CI 0.51 to 0.66), respectively. Compared to a reference A1C level of <7%, the risk estimates of increasing A1C levels (7.0-7.9, 8.0-8.9 and ≥9%) steadily decreased with adj. ORs of 0.79 (95% CI 0.72 to 0.86), 0.63 (95% CI 0.55 to 0.72), and 0.46 (95% CI 0.40 to 0.53), respectively. Neither use of insulin, metformin, nor sulfonylureas was associated with an altered risk of incident gout. CONCLUSIONS Increased A1C levels, but not use of antidiabetic drugs, was associated with a decreased risk of incident gout among patients with T2DM.

Effect of large doses of parenteral vitamin D on glycaemic control and calcium/phosphate metabolism in patients with stable type 2 diabetes mellitus: a randomised, placebo-controlled, prospective pilot study.

OBJECTIVE Vitamin D (D₃) status is reported to correlate negatively with insulin production and insulin sensitivity in patients with type 2 diabetes mellitus (T2DM). However, few placebo-controlled intervention data are available. We aimed to assess the effect of large doses of parenteral D3 on glycosylated haemoglobin (HbA(₁c)) and estimates of insulin action (homeostasis model assessment insulin resistance: HOMA-IR) in patients with stable T2DM. MATERIALS AND METHODS We performed a prospective, randomised, double-blind, placebo-controlled pilot study at a single university care setting in Switzerland. Fifty-five patients of both genders with T2DM of more than 10 years were enrolled and randomised to either 300,000 IU D₃ or placebo, intramuscularly. The primary endpoint was the intergroup difference in HbA(₁c) levels. Secondary endpoints were: changes in insulin sensitivity, albuminuria, calcium/phosphate metabolism, activity of the renin-aldosterone axis and changes in 24-hour ambulatory blood pressure values. RESULTS After 6 months of D₃ supply, there was a significant intergroup difference in the change in HbA(₁c) levels (relative change [mean ± standard deviation] +2.9% ± 1.5% in the D₃ group vs +6.9% ± 2.1% the in placebo group, p = 0.041) as HOMA-IR decreased by 12.8% ± 5.6% in the D₃ group and increased by 10% ± 5.4% in the placebo group (intergroup difference, p = 0.032). Twenty-four-hour urinary albumin excretion decreased in the D₃ group from 200 ± 41 to 126 ± 39, p = 0.021). There was no significant intergroup difference for the other secondary endpoints. CONCLUSIONS D₃ improved insulin sensitivity (based on HOMA-IR) and affected the course of HbA(₁c) positively compared with placebo in patients with T2DM.

Impaired glucose metabolism and type 2 diabetes in apparently healthy senior citizens

STUDY PRINCIPLE To estimate the prevalence of unknown impaired glucose metabolism, also referred to as prediabetes (PreD), and unknown type 2 diabetes mellitus (T2DM) among subjectively healthy Swiss senior citizens. The fasting plasma glucose (FPG) and glycated haemoglobin A1c (HbA1c) levels were used for screening. A total of 1 362 subjects were included (613 men and 749 women; age range 60-99 years). Subjects with known T2DM were excluded. METHODS The FPG was processed immediately for analysis under standardised preanalytical conditions in a cross-sectional cohort study; plasma glucose levels were measured by means of the hexokinase procedure, and HbA1c was measured chromatographically and classified using the current American Diabetes Association (ADA) criteria. RESULTS The crude prevalence of individuals unaware of having prediabetic FPG or HbA1c levels, was 64.5% (n = 878). Analogously, unknown T2DM was found in 8.4% (n = 114) On the basis of HbA1c criteria alone, significantly more subjects with unknown fasting glucose impairment and laboratory T2DM could be identified than with the FPG. The prevalence of PreD as well as of T2DM increased with age. The mean HOMA indices (homeostasis model assessment) for the different age groups, between 2.12 and 2.59, are consistent with clinically hidden disease and are in agreement with the largely orderly Body Mass Indices found in the normal range. CONCLUSIONS Laboratory evidence of impaired glucose metabolism and, to a lesser extent, unknown T2DM, has a high prevalence among subjectively healthy older Swiss individuals. Laboratory identification of people with unknown out-of-range glucose values and overt diabetic hyperglycaemia might improve the prognosis by delaying the emergence of overt disease.

Treatment intensification with insulin glargine in patients with inadequately controlled type 2 diabetes improves glycaemic control with a high treatment satisfaction and no weight gain

PRINCIPLES We aimed to evaluate the efficacy of, and treatment satisfaction with, insulin glargine administered with SoloSTAR® or ClikSTAR® pens in patients with type 2 diabetes mellitus managed by primary care physicians in Switzerland. METHODS A total of 327 patients with inadequately controlled type 2 diabetes were enrolled by 72 physicians in this prospective observational study, which aimed to evaluate the efficacy of a 6-month course of insulin glargine therapy measured as development of glycaemic control (glycosylated haemoglobin [HbA1c] and fasting plasma glucose [FPG]) and weight change. We also assessed preference for reusable or disposable pens, and treatment satisfaction. RESULTS After 6 months, the mean daily dose of insulin glargine was 27.7±14.3 U, and dose titration was completed in 228 (72.4%) patients. Mean HbA1c decreased from 8.9%±1.6% (n=327) to 7.3%±1.0% (n=315) (p<0.0001), and 138 (43.8%) patients achieved an HbA1c≤7.0%. Mean FPG decreased from 10.9±4.5 to 7.3±1.8 mmol/l (p<0.0001). Mean body weight did not change (85.4±17.2 kg vs 85.0±16.5 kg; p=0.11). Patients' preference was in favour of the disposable SoloStar® pen (80%), as compared with the reusable ClickStar® pen (20%). Overall, 92.6% of physicians and 96.3% of patients were satisfied or very satisfied with the insulin glargine therapy. CONCLUSIONS In patients with type 2 diabetes insulin glargine administered by SoloSTAR® or ClikSTAR® pens, education on insulin injection and on self-management of diabetes was associated with clinically meaningful improvements in HbA1c and FPG without a mean collective weight gain. The vast majority of both patients and primary care physicians were satisfied with the treatment intensification.

Prevalence and determinants of type 2 diabetes among Filipino Americans in Houston metropolitan statistical area, Texas

Diabetes in adults (type 2) has emerged as a world health problem. Prevalence and risk factors have been found to vary in different populations. The wide range of prevalence rates worldwide indicates the importance of genetic and environmental factors in the etiology of the disease. The few available studies suggest that Filipinos are among the higher-risk groups for developing diabetes. This cross-sectional study estimated the overall prevalence rate of type 2 diabetes among Filipino Americans, ages 20–74 years and residents of Houston Metropolitan Statistical Area, Texas, to be 16.1%. The observed high prevalence was associated with age, sex, family history of diabetes, obesity, region of birth; and, in women, gestational diabetes and income. The diabetic Filipino Americans had a higher proportion of parental history of diabetes, medical history of hypertension, and history of smoking; were physically less active, but generally non-obese, compared with the United States diabetic population. ^