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Aim: To explore the glycemic characteristics of non-diabetic shift workers and associations with metabolic indices. Methods: In this cross-sectional study, 450 non-diabetic males, including 238 shift workers, aged 23–58 years, were recruited after a screening oral glucose tolerance test. Blood samples and anthropometric data were collected. Hundred and fifty of them finished a continuous glucose monitoring for 3–7 days. Results: Compared to daytime workers, shift workers presented with larger WHR (p < 0.001), higher HOMA-IR (p < 0.001), higher hs-CRP level (p < 0.001) and worse lipid profiles. In glycemic characteristics, shift workers with normal glucose regulation had a similar mean blood glucose (MBG), daytime MBG, percentage of time of hyperglycemia, hypoglycemia, euglycemia, and fluctuation parameters, including standard deviation of blood glucose (SDBG), mean amplitude of glycemic excursions (MAGE) and mean of daily differences (p > 0.05, respectively), while they had a higher nighttime MBG (p = 0.026) and blood glucose (BG) at 3 a.m. (p = 0.015). For subjects with impaired glucose regulation, both groups had no difference in any clinical characteristics or glycemic parameters (p > 0.05, respectively). Further regression analysis revealed the association between MBG/SDBG/MAGE/nighttime MBG/BG at 3 a.m. and age/WHR/hs-CRP/TC. Conclusion: For non-diabetic shift workers, the glycemic characteristic was the elevated nighttime glycemia, presented as higher nighttime MBG and BG at 3 a.m. And both metrics were closely associated with central obesity. Elevated nighttime glycemia was an early signal of glucose metabolism disorder in shift workers. [ABSTRACT FROM AUTHOR]

Aims: Inflammation plays a role in the development and progression of type 2 diabetes macroangiopathy. Interleukin 33 (IL-33) drives production of Th2-associated cytokines. The soluble form of suppression of tumorigenicity 2 (sST2) acting as a decoy receptor blocks IL-33 and tones down Th2 inflammatory response. We investigated the role of sST2 as a predictor of CV and all-cause mortality in a cohort of patients affected by established atherosclerotic disease.Methods: 399 patients with atherosclerotic disease from the Tor Vergata Atherosclerosis Registry performed follow-up every year by phone interview. The primary endpoint was cardiovascular death and the secondary endpoint was death for any other disease.Results: sST2 plasma levels were significantly increased from normal glucose-tolerant patients to patients with history of type 2 diabetes (p < 0.00001). Levels of sST2 were significantly correlated with fasting plasma glucose (R = 0.16, p = 0.002), HbA1c (R = 0.17, p = 0.002), and HOMA (R = 0.16, p = 0.004). Dividing patients in tertiles of sST2 levels, those belonging to the highest tertile showed an increased rate of all-cause and cardiovascular mortality, (all-cause mortality p = 0.045 and CVD mortality p = 0.02). A multivariate Cox analysis revealed that sST2 increased the risk in cardiovascular mortality per SD by hazard ratio 1.050 (95% CI 1.006-1.097, p = 0.025) after adjustment for age and hs-CRP while it did not significantly change the risk for all-cause mortality.Conclusions: High circulating level of sST2 is associated to increased CVD mortality and markers of metabolic dysfunction in subjects with atherosclerotic disease. [ABSTRACT FROM AUTHOR]

Despite a clear association between type 2 diabetes (T2D) and fracture risk, the pathogenesis of bone fragility in T2D has not been clearly elucidated. Insulin resistance is the primary defect in T2D. Insulin signalling regulates both bone formation and bone resorption, but whether insulin resistance can affect bone has not been established. On the other hand, evidence exists that bone might play a role in the regulation of glucose metabolism. This article reviews the available experimental and clinical evidence on the interplay between bone and insulin resistance. Interestingly, a bilateral relationship between bone and insulin resistance seems to exist that unites them in a biological partnership. [ABSTRACT FROM AUTHOR]

Aims: Although it is widely accepted that diabetic polyneuropathy (DPN) is linked to a marked decline in neuromuscular performance, information on the possible impact of type 1 diabetes (T1D) on muscle strength and fatigue remains unclear. The purpose of this study was to investigate the effects of T1D and DPN on strength and fatigability in knee extensor muscles. Methods: Thirty-one T1D patients (T1D), 22 T1D patients with DPN (DPN) and 23 matched healthy control participants (C) were enrolled. Maximal voluntary contraction (MVC) and endurance time at an intensity level of 50% of the MVC were assessed at the knee extensor muscles with an isometric dynamometer. Clinical characteristics of diabetic patients were assessed by considering a wide range of vascular and neurological parameters. Results: DPN group had lower knee extensor muscles strength than T1D (−19%) and the C group (−37.5%). T1D group was 22% weaker when compared to the C group. Lower body muscle fatigability of DPN group was 22 and 45.5% higher than T1D and C group, respectively. T1D group possessed a higher fatigability (29.4%) compared to C group. A correlation was found between motor and sensory nerve conduction velocity and muscle strength and fatigability. Conclusions: Patients with T1D are characterised by both a higher fatigability and a lower muscle strength, which are aggravated by DPN. Our data suggest that factors other than nervous damage play a role in the pathogenesis of such defect. [ABSTRACT FROM AUTHOR]

Aims: Quality of life is a major focus of health care today. In published studies on patients with type 2 diabetes, findings on quality of life are mixed. Those with diabetes have chronic illness and must adhere to a complicated care regimen daily, which for many patients is challenging. This study analyzed psychosocial factors and metabolic control as potential predictors of quality of life among these patients. Methods: A cross-sectional study of 397 patients with type 2 diabetes was conducted in a hospital in Nanjing, China. Demographic information and clinical characteristics were collected from the medical record. The World Health Organization Quality of Life-BREF, General Self-Efficacy Scale, Diabetes Distress Scale, and Diabetes Empowerment Scale-Short Form were administered. Results: The mean score of quality of life was 67.80 ± 13.44 on a 100-point scale. General self-efficacy ( β = 0.340, P < 0.001), diabetes distress ( β = −0.266, P < 0.001), and diabetes empowerment ability ( β = 0.207, P < 0.001) were predictors of quality of life. In contrast, other factors including HbA1c, diabetes complications, and the duration of diabetes were not associated with quality of life ( P > 0.05). Conclusions: Our study indicated that psychosocial factors such as self-efficacy, diabetes distress, and diabetes empowerment ability are related to quality of life. Assessment and interventions aimed at reducing psychosocial problems should be applied in diabetes care. [ABSTRACT FROM AUTHOR]

Aims: To evaluate the effect of cumulative smoking on the development of diabetic nephropathy. Methods: Study included 3613 patients with type 1 diabetes, participating in the Finnish Diabetic Nephropathy Study. The 12-year cumulative risk of microalbuminuria, macroalbuminuria and end-stage renal disease (ESRD) was estimated for current, ex- and nonsmokers. Cox regression analyses, with multivariable adjustments for other risk factors for diabetic nephropathy, were used to evaluate the risk at different stages of diabetic nephropathy based on the cumulative amount of smoking in pack-years. Results: The 12-year cumulative risk of microalbuminuria was 18.9 % (95 % CI 14.6-23.0, P < 0.0001) for current smokers and 15.1 % (10.3-19.6, P = 0.087) for ex-smokers, compared with 10.0 % (7.8-12.1) for nonsmokers. The corresponding risks of macroalbuminuria were 14.4 % (95 % CI 10.8-17.9, P < 0.0001), 6.1 % (3.5-8.6, P = 0.082) and 4.7 % (3.0-6.4), respectively. The 12-year cumulative risk of ESRD was 10.3 % (95 % CI 8.4-12.4, P < 0.0001) for current smokers and 10.0 % (7.9-12.3, P < 0.0001) for ex-smokers, compared with 5.6 % (4.6-6.7) for nonsmokers. In the current smokers, one pack-year increased the risk of macroalbuminuria with a HR of 1.025 (1.010-1.041) and the risk of ESRD with a HR of 1.014 (1.001-1.026) compared with nonsmokers, in the fully adjusted model. In the ex-smokers, the risk of macroalbuminuria and ESRD was no different from the risk in nonsmokers after multivariable adjustment. Conclusions: Current smoking is a risk factor for the progression of diabetic nephropathy and the risk increases with the increasing dose of smoking. Ex-smokers seem to carry a similar risk of progression of diabetic nephropathy as nonsmokers. [ABSTRACT FROM AUTHOR]

Aims: The aim of the current study was to characterize β-cell function, insulin sensitivity and line of inheritance in patients with recent-onset type 2 diabetes of Yemenite and non-Yemenite Jewish origin. Methods: A cohort study including 121 GAD negative diabetic patients, 59 of Yemenite and 62 of non-Yemenite origin, treated by diet ± oral antihyperglycemic monotherapy who underwent 180-min meal tolerance test (MMT). Based on MMT, indexes of insulin resistance and secretion were calculated. Results: There were no significant differences in age, sex, diabetes duration, BMI, HbA1c and lipid profile. A significant difference was found in family history of diabetes: 63 % of patients of Yemenite origin had maternal inheritance versus 35 % in the non-Yemenite origin ( p < 0.001). Both indexes of β-cell function, the insulinogenic and the disposition indexes were significantly lower in patients of Yemenite origin compared with non-Yemenite origin (0.66 ± 0.4 vs. 0.93 ± 0.8, p = 0.04; 2.3 ± 1.8 vs. 3.3 ± 3.3, p = 0.04, respectively) with no difference in insulin sensitivity. When females and males were analyzed separately, the difference in maternal inheritance remained significant in both, but the difference in β-cell function indexes was observed only in males ( p = 0.03, p = 0.01, respectively). Conclusions: Males with recent-onset diabetes of Yemenite origin have a significant reduction of β-cell function and reduced ability to compensate for insulin resistance compared with diabetic males of non-Yemenite origin. Both males and females of Yemenite origin have a significantly higher maternal inheritance of diabetes. These data suggest different underlying mechanisms leading to early loss of β-cell in diabetic males of Yemenite origin. [ABSTRACT FROM AUTHOR]

Aims: Patients with diabetes had a higher risk of developing depressive symptoms. Little is known about the risk of depressive symptoms associated with different glucose metabolism status. We performed a meta-analysis of prospective cohort studies to investigate the risk of depressive symptoms among individuals with impaired glucose metabolism (IGM), newly diagnosed diabetes (NDM), and previously diagnosed diabetes (PDM), compared with those with normal glucose metabolism (NGM), and further examined the influence of diabetes-related comorbidities on the association. Methods: PubMed and EMBASE were searched for relevant studies through 5 September 2015. The random-effects model was used to calculated overall relative risk (RR) and confidence interval (CI). Three separated meta-analyses were conducted by estimating the risk of depressive symptoms among people with IGM, NDM, and PDM, with NGM as a common reference category. Secondary analyses were conducted to examine whether adjustment for diabetes-related comorbidities affected the association. Results: Five prospective cohort studies were included in the analyses, with a total of 18,051 participants involved. People with IGM (RR = 1.08, 95 % CI 0.84-1.38) and NDM (RR = 1.07, 95 % CI 0.74-1.55) were not associated with risk of developing depressive symptoms, whereas patients with PDM were associated with a modest increased risk of depressive symptoms (RR = 1.29, 95 % CI 1.03-1.63), after adjustment for demographic/socioeconomic factors. The risk of depressive symptoms associated with PDM was attenuated to be non-significant after pooling RRs that were adjusted for diabetes-related comorbidities. Conclusions: Our meta-analysis suggested people with PDM, but not IGM or NDM had an increased risk of developing depressive symptoms, and the risk was partially explained by diabetes-related comorbidities. Our findings indicated that routine diabetes care should put more emphasis on psychological problems of diabetic patients with complications. [ABSTRACT FROM AUTHOR]

Aims: To address questions regarding onset and progression of types 1 and 2 diabetes (T1D/T2D), surrogate imaging biomarkers for beta cell function and mass are needed. Here, we assess the potential of GPR44 as a surrogate marker for beta cells, in a direct comparison with clinically used biomarker VMAT2. Methods: GPR44 surface availability was assessed by flow cytometry of human beta cells. RNA transcription levels in different pancreas compartments were evaluated. The density of GPR44 receptor in endocrine and exocrine tissues was assessed by the radiolabeled GPR44 ligand [H]AZD 3825. A direct comparison with the established beta cell marker VMAT2 was performed by radiolabeled [H]DTBZ. Results: GPR44 was available on the cell surface, and pancreatic RNA levels were restricted to the islets of Langerhans. [H]AZD 3825 had nanomolar affinity for GPR44 in human islets and EndoC-βH1 beta cells, and the specific binding to human beta cells was close to 50 times higher than in exocrine preparations. The endocrine-to-exocrine binding ratio was approximately 10 times higher for [H]AZD 3825 than for [H]DTBZ. Conclusion: GPR44 is a highly beta cell-specific target, which potentially offers improved imaging contrast between the human beta cell and the exocrine pancreas. [ABSTRACT FROM AUTHOR]

Aims: Recent studies in mouse models of T2D showed that interleukin-6 (IL-6), released from skeletal muscle, is associated with increased glucose-dependent insulin secretion. Few data currently exist exploring the relationship between IL-6 and beta-cell function in humans. We investigated whether IL-6 is positively associated with beta-cell function in newly diagnosed T2D. We extended the same analyses to IL-10, because it regulated similarly to IL-6 in skeletal muscle, and TNF-α and C-reactive protein (CRP), as general biomarkers of inflammation. Methods: In 330 VNDS participants, we assessed (1) basal plasma concentrations of IL-6, IL-10, TNF-α, and CRP; (2) beta-cell function, estimated by OGTT minimal modeling and expressed as derivative (DC) and proportional control (PC); (3) insulin sensitivity, by euglycemic insulin clamp. Results: IL-6 was positively associated with PC in both univariate analysis ( p = 0.04) and after adjustment for age, sex, BMI, HbA1c, and M-clamp ( p = 0.01). HbA1c was the major independent contributor to the overall variance of PC (16 %), followed by BMI and IL-6 (~2 % each). Similar results were obtained for IL-10 ( p = 0.048, univariate; p = 0.04, fully adjusted). TNF-α and CRP were not significantly associated with any component of beta-cell function. Conclusions: Our data are the first evidence in human subjects that an endocrine loop involving IL-6 may act as positive modulator of glucose-dependent insulin secretion. Further functional studies are needed to corroborate IL-6 system as a potential druggable target in diabetes. Clinical trial registration number: NCT01526720 (). [ABSTRACT FROM AUTHOR]

The population attributable fraction (PAF) of risk factors for the worsening of glucose metabolism in subjects with normal glucose tolerance (NGT) has not been calculated. Our aim was to obtain the PAF of increased body mass index (BMI) and attenuated beta-cell function (BCF) on worsening of glucose metabolism in subjects with NGT. We longitudinally analyzed 604 Japanese adults. The follow-up glucose tolerance status was determined 3.7 years later: 430 participants remained in the NGT category and 102 had progressed to impaired fasting glucose, 67 to impaired glucose tolerance, and 5 to diabetes mellitus. A product of ISI and Stumvoll-1, i.e., oral disposition index (DI), was used as a measure of BCF. The optimal cutoff baseline BMI and DI values for the prediction of the worsening of glucose metabolism were > 23.1 and < 7.299 kg/m, respectively. Isolated increased BMI (iBMI), isolated low DI (iDI), and 'BMI and DI (BMI/DI)' were all independently related to the worsening, and the PAF values (95 % CI) for worsening due to iBMI, iDI, and BMI/DI were 12.9 (3.2-18.4) %, 10.9 (5.0-13.9) %, and 31.4 (22.7-36.3) %, respectively. As much as 55 % of the worsening of glucose metabolism in the NGT subjects was attributable to increased BMI and/or attenuated BCF. The optimal cutoff for BMI was as low as 23.1 kg/m in this population. We believe that these data should form the basis of future public health strategies for the prevention of diabetes in Japan. [ABSTRACT FROM AUTHOR]

Hypoglycemia increases the risk for both overall and sudden death. At a cellular level, hypoglycemia causes alterations in the physiology of myocardial tissue that are identical to proarrhythmic medications. Reduced serum glucose blocks the repolarizing K channel HERG, which leads to action potential and QT prolongation and is uniformly associated with risk for torsades de pointes ventricular tachycardia. The sympathetic response induced by hypoglycemia also increases the risk of arrhythmias from Ca overload, which occur with sympathomimetic medications and excessive beta adrenergic stimulation. Thus, hypoglycemia can be considered a proarrhythmic event. This review focuses on emerging evidence for two other important changes induced by hypoglycemia that promote arrhythmias: ischemia and bradycardia. Studies of patients with 'insulin shock' therapy from the early twentieth century and other more recent data strongly suggest that hypoglycemia can cause ischemia of myocardial tissue, both in association with coronary artery obstructions and by cellular mechanisms. Ischemia induces multiple proarrhythmic responses. Since ischemia itself reduces the possibility of using energy substrates other than glucose, hypoglycemia may generate positive feedback for electrophyisologic destabilization. Recent studies also show that hypoglycemia can cause bradycardia and heart block. Bradycardia is known to cause action potential prolongation and potentiate the development of torsades de pointes, particularly with low-serum K which can be induced by hypoglycemic episodes. Thus, hypoglycemia-induced bradycardia may also create a dynamic, positive feedback for the development of arrhythmias and sudden death. These studies further support the hypothesis that hypoglycemia is a proarrhythmic event. [ABSTRACT FROM AUTHOR]

Inflammatory markers are elevated in type 2 diabetic patients (DP) and may predict the development of type 2 diabetes. Our aims were to analyze differences in the expression of inflammatory and immunological molecules between DP and healthy subjects and to investigate whether glycemic control might prevent the overexpression of inflammatory markers in DP. Twenty-two DP with advanced atherosclerosis and eight healthy blood donors were included. DP were classified as well (HbA ≤ 6.5) or poorly controlled (HbA > 6.5). In 'in vitro' studies, monocytes were exposed to low (5.5 mM) or high glucose (26 mM) concentrations in the absence or presence of insulin. Expression profiling of 14 inflammatory genes was analyzed using TLDA analysis. 'In vivo' results show that monocytes from DP had increased levels of monocyte chemoattractant protein (MCP-1) and interleukin 6 (IL6) and lower levels of Toll-like receptor 2 (TLR2) mRNA than healthy subjects. Well-controlled DP had lower levels of IL-6 than poorly controlled DP, suggesting that glycemic control may prevent IL6 mRNA alterations associated with diabetes. 'In vitro' results demonstrate that glucose directly and significantly induced MCP-1 and IL6 and reduced TLR2 mRNA expression. Insulin at high dose (100 IU/ml) dramatically enhanced the upregulatory effects of glucose on MCP-1 and IL-6 and reduced per se TLR2 mRNA expression. MCP-1, IL-6 and TLR2 are key inflammatory players altered in monocytes from type 2 DP. Both hyperinsulinemia and hyperglycemia contribute to alter the expression of these genes. The glycemic control only significantly prevented IL6 overexpression in this group of patients. [ABSTRACT FROM AUTHOR]