Diabetes Mellitus, Type 2
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Pubmed
Journal: Revista espanola de cardiologia
August/4/2009
Abstract

OBJECTIVE

Although type-2 diabetes is a well-known cause of death, the mortality associated with undiagnosed diabetes and early-stage dysglycemia has not been clearly determined.

METHODS

This study included 1015 individuals aged 30-75 years who took part in the first phase of the Asturias study (1998-1999). Participants completed a questionnaire and underwent a physical examination and an oral glucose tolerance test (OGTT). All deaths that occurred in the cohort within 6 years of follow-up (i.e. December 1998 to December 2004) were recorded.

RESULTS

Participants were divided into four groups according to the condition indicated by their OGTT result in the first phase of the study: normoglycemia, pre-diabetes, undiagnosed diabetes or diagnosed diabetes (World Health Organization 1999 criteria). A total of 42 deaths were recorded during follow-up. With normoglycemic individuals acting as a control group, multivariate analysis showed that the relative risk of mortality was 2.5 (95% CI, 1-6.3) in the group with diagnosed diabetes, 2.7 (95% CI, 1.1-6.7) in the group with undiagnosed diabetes and 1.6 (95% CI, 0.7-4) in the group with pre-diabetes.

CONCLUSIONS

Both individuals with diagnosed diabetes and those with undiagnosed diabetes had a risk of mortality around 2.5-3 times greater than individuals with normoglycemia. Those with pre-diabetes also had increased mortality relative to the control group, though the difference was not significant.

Pubmed
Journal: Diabetes care
July/15/1990
Abstract

Various parameters of coagulation and fibrinolysis were measured in 13 men (aged 54 +/- 3 yr) with non-insulin-dependent diabetes mellitus (NIDDM) before and after 12-14 wk of exercise training. Subjects exercised for 30 min 3 times/wk at 70% of maximum O2 consumption (VO2max). Training increased VO2max by 12.5% but did not alter body weight, relative body fat, blood pressure, cholesterol, triglycerides, or high-density lipoprotein cholesterol. Slight downward trends were apparent for fasting glucose and insulin, but glycosylated hemoglobin was unchanged. There were no changes in coagulation parameters of plasminogen, hematocrit, or alpha 2-antiplasmin. Plasma fibrinogen (303 +/- 24.2 vs. 256 +/- 12.3 mg/dl) and fibronectin (380 +/- 41.9 vs. 301 +/- 22.2 micrograms/ml) were significantly reduced (P less than 0.02) by exercise conditioning. Three assays of fibrinolytic activity (tissue plasminogen activator, euglobulin lysis time, and an isotopic measure of fibrinolysis) confirmed that neither basal fibrinolysis nor the fibrinolytic responses to venous occlusion and maximal exercise were significantly altered. Exercise conditioning may have antithrombotic effects in NIDDM by reducing plasma fibrinogen and fibronectin. Although the significance of the fall in fibronectin awaits further studies, the reduction in plasma fibrinogen gives a rationale for the use of exercise training in men with NIDDM.

Pubmed
Journal: Atherosclerosis
January/19/2004
Abstract

OBJECTIVE

Hyperhomocysteinemia is a risk factor for atherothrombosis. Through unknown mechanisms, individuals with type 2 diabetes appear particularly susceptible. We determined whether components of homocysteine metabolism are associated with intima-media thickness in individuals with and without type 2 diabetes.

RESULTS

In a cross-sectional design, we studied 231 Caucasian individuals, 60.6% having type 2 diabetes. We measured fasting homocysteine, vitamin B6 and vitamin B12 in plasma, and folate, S-adenosylmethionine and S-adenosylhomocysteine in plasma and erythrocytes. A homocysteine concentration >12 micromol/l was associated with a greater intima-media thickness of +0.07 mm (95% CI, +0.01 to +0.13; P=0.03) among diabetic individuals and of -0.004 mm (95%CI, -0.08 to +0.07; P=0.92) among non-diabetic individuals. An erythrocyte S-adenosylmethionine concentration above >4000 nmol/l was associated with a smaller intima-media thickness of -0.04 mm (95%CI, -0.10 to +0.02; P=0.17) for diabetic individuals versus -0.12 mm (95%CI, -0.20 to -0.36; P=0.005) for non-diabetic individuals.

CONCLUSIONS

With regard to carotid intima-media thickness, individuals with diabetes appear more susceptible to the detrimental effects of homocysteine than non-diabetic individuals. In addition, diabetic individuals may lack the protective effect on the vascular wall conferred by high concentrations of S-adenosylmethionine. These findings may help explain why hyperhomocysteinemia is an especially strong risk factor for atherothrombosis among individuals with type 2 diabetes.

Pubmed
Journal: The Kaohsiung journal of medical sciences
September/22/2003
Abstract

The effects of substances extracted from Toona sinensis leaves, using 50% alcohol/water, on cellular [3H]-2-deoxyglucose uptake in differentiated cultured 3T3-L1 adipocytes were investigated. Following treatment of cells with 0.001, 0.01, or 0.1 mg/mL extracts for 60 minutes, [3H]-2-deoxyglucose uptake increased from a basal value of 0.23 nmol/min/mg protein to 0.30, 0.33, and 0.38 nmol/min/mg protein, respectively. In insulin-stimulated cells, cellular [3H]-2-deoxyglucose uptake was enhanced by Toona sinensis leaf extract from a basal value of 0.35 nmol/min/mg protein to 0.41, 0.46, and 0.52 nmol/min/mg protein, respectively. Cellular glucose uptake was also enhanced by Toona sinensis leaf extract after incubation of cells with 20 mM glucose for 48 hours. Cellular glucose uptake with a combination of Toona sinensis leaf extract and insulin was significantly inhibited by pretreatment of cells with the protein synthesis inhibitor cycloheximide and the protein kinase C inhibitor calphostin C in normal-, medium- and high-glucose media. However, the glucose uptake-enhancing effect of Toona sinensis leaf extract was not diminished by cycloheximide and calphostin C in the absence of insulin. These results indicate that enhancement of cellular glucose uptake by Toona sinensis leaf extract in basal and insulin-stimulated 3T3-L1 adipocytes may be mediated by distinct mechanisms.

Pubmed
Journal: Diabetes research and clinical practice
November/4/1998
Abstract

BACKGROUND

The association between diabetes, glycaemic control and the prevalence of infections seems obvious to most general practitioners. However, this association is still not very clear.

OBJECTIVE

The aim of this study in general practice was to investigate which infections patients with treated type 2 diabetes present to their general practitioner, and to study whether a relationship exists between glycaemic status and these infections.

METHODS

Over a period of 2 years eight fasting glucose and glycosylated haemoglobin values were related to the presented infections in 328 patients.

RESULTS

193 patients presented with one or more infections (a total of 458 infections, with a mean of 2.4 (+/- 1.9) infections). Patients with and without infections did not differ in mean glycosylated haemoglobin and fasting glucose levels. There was no difference in presentation of infections between well controlled and less controlled patients. However, patients who presented with an infection showed significantly higher mean glycosylated haemoglobin levels in that period compared to the mean levels in periods without any infection.

CONCLUSIONS

Considering the limitations of this study, hyperglycaemia is more likely a result of than a cause of common infections.

Pubmed
Journal: Diabetes care
October/26/1998
Abstract

The sympathoadrenal system plays an important role in the regulation of metabolic and cardiovascular activity. With respect to carbohydrate metabolism, specifically, catecholamines affect both insulin secretion and insulin action. Alterations in sympathoadrenal system function have been suggested to contribute to the constellation of disorders referred to as syndrome X (obesity, hypertension, NIDDM, and dyslipoproteinemia). The origin of any such abnormalities in sympathoadrenal function is unknown. The sympathoadrenal system, like other parts of the mammalian nervous system, is susceptible to environmental influences during development. Although these neurological alterations in rats are particularly prominent during the postpartum period, they are also apparent during intrauterine life. Moreover, the effects of these early environmental factors last well into adulthood and may represent permanent alterations in sympathetic nervous system behavior. Although the impact of maternal diabetes on sympathetic neural development has not been examined extensively, limited data available indicate that maternal diabetes may affect sympathetic nervous system development in the offspring. Although the full impact of maternal diabetes on neurological development in the offspring is unknown, given the myriad effects of the sympathoadrenal system on mammalian physiology, lasting changes in autonomic nervous system function may have potentially profound consequences for metabolic and cardiovascular regulation in adulthood.

Pubmed
Journal: Clinical neurology and neurosurgery
July/14/2009
Abstract

We report a 57-year-old woman with uremic encephalopathy who presented with dysarthria, dysphagia, hypophonia, and drowsiness. The patient's radiologic findings were rather unusual in that magnetic resonance imaging (MRI) showed abnormal findings involving the basal ganglia bilaterally and frontal cortex unilaterally. After intensified hemodialysis, her symptoms and follow-up brain MRI showed marked improvement. We postulated that the underlying mechanism of uremic encephalopathy based on diffusion-weighted imaging and apparent diffusion coefficient maps.

Pubmed
Journal: ILAR journal
August/2/2006
Abstract

Although the epidemiology of type 2 diabetes (T2D) has been well described, there is much about the disease that remains unclear. For example, lifestyle factors-including increased body weight with visceral fat deposition and insufficient physical activity-are thought to be primary contributors to the adverse changes in the metabolism of muscle and fat cells that comprise the first stage of the disease. However, the precise mechanisms underlying these initial alterations are incompletely understood. Other, less obvious questions relate to the presence of sex differences in the development and health consequences of T2D, the etiological role of the central nervous system ("stress"), and the potential evolutionary origins of T2D susceptibility. Some of these issues can be resolved by further study of human populations. However, many questions can be answered only through the kinds of controlled prospective studies that are conducted with appropriate animal models. The use of such models can be an invaluable part of an overall strategy designed to elucidate the mechanisms underlying the development of T2D, understand the natural history of the disease, identify targets for therapy, and evaluate interventions. Current evidence indicates that no single animal model replicates the development of human T2D in all of its details. Nonetheless, the existing models (e.g., naturally occurring and genetically modified rodents, cats, pigs, and nonhuman primates) offer researchers a rich array of opportunities to investigate the myriad complexities of T2D. The individual contributions comprising this issue of ILAR Journal review the research that has been conducted on many of these animals.

Pubmed
Journal: Bioscience, biotechnology, and biochemistry
March/13/1997
Abstract

The hypoglycemic effects of Lagerstroemia speciosa L., known by the Tagalog name of banaba in the Phillipines, were studied using hereditary diabetic mice (Type II, KK-AY/Ta Jcl). The mice were fed a test diet containing 5% of the hot-water extract (HWE) from banaba leaves, 3% of the water eluent of the partial fraction unadsorbed onto HP-20 resin of HWE (HPWE), and 2% of the methanol eluent of the partial fraction adsorbed onto HP-20 resin of it (HPME) for a feeding period of 5 weeks. The elevation of blood plasma glucose level in non-insulin dependent diabetic mice fed the cellulose as control (CEL) diet were almost entirely suppressed by addition of either HWE or HPME in place of cellulose in the CEL diet. Water intakes were inclined to increase gradually in the group fed either CEL or HPWE, but lower in the mice fed either HWE or HPME than in the animals given either CEL or HPME. The level of serum insulin and the amount of urinary excreted glucose were also lowered in mice fed HWE. Plasma total cholesterol level was also lowered in mice fed the either HWE or HPME. It is suggested that HWE, especially HPME, obtained from banaba leaves have beneficial effects on control of the level of plasma glucose in non-insulin dependent diabetes mellitus.

Pubmed
Journal: Diabetes, obesity & metabolism
August/20/2006
Abstract

The early stages of type 2 diabetes mellitus are characterized by the development of insulin resistance (IRe) in muscle cells and adipocytes with the concomitant loss of beta-cell compensation. We have extensively reviewed the literature related to metabolic and signalling pathways of reactive oxygen species (ROS) in regard to the coordinated development of oxidative stress and IRe. We considered the hypothesis that oxidative stress leads to IRe in muscle cells and adipocytes, but found that the data are more consistent with the hypothesis that the cellular mechanisms that protect against oxidative stress per se are capable of creating an ROS-dependent insulin-resistant state. Furthermore, ROS-induced mitochondrial dysfunction can lead to disruptions of lipid metabolism, increasing the intracellular lipid content, and, in addition, contribute to lipid-dependent IRe in myocytes. Together, these two ROS-activated pathways to IRe can contribute to a global state of profound resistance to insulin action. Therapeutic strategies should, therefore, be directed towards reducing insulin resistance without an increase in ROS production or concentration. Pharmacological or other approaches to IRe that result in the activation of mitochondrial biogenesis in particular could be highly beneficial in the prevention or treatment of both insulin resistance and type 2 diabetes.

Pubmed
Journal: Hypertension research : official journal of the Japanese Society of Hypertension
April/18/2015
Abstract

The aim of this study was to evaluate the reliability of self-reported home blood pressure (HBP) in patients with type 2 diabetes by comparing the self-reported values with HBP measurements stored in the memory of the blood pressure (BP) monitor. We also examined what factors affect the reliability of HBP measurements. A cross-sectional study was conducted in 280 patients with type 2 diabetes. Patients were requested to perform triplicate morning and evening measurements over a span of 2 weeks and to enter their HBP values into logbooks. Patients were not informed about the memory function of their BP monitoring devices. The concordance rate of HBP reporting was 78.6%. A total of 51.4% of patients (n=144) had >90% concordant data, and 15.7% of patients (n=44) had ⩽50% concordant data. In general, HBP values from the logbook were significantly lower and less variable than those from the stored memory (P<0.05). The most common type of incorrect data was selected data that were reported in the logbooks that were randomly selected from multiple readings by the HBP monitors (55.8%). The concordance rate of HBP reporting significantly correlated with hemoglobin A1c levels (β=-0.156; P=0.0149) and with smoking status (current vs. never, β=-0.165; P=0.0184). In conclusion, HBP measurements from the patients' logbooks were lower and less variable than those from the stored memory in the BP monitors of patients with type 2 diabetes, and the reliability of HBP reporting was affected by glycemic control and smoking status. Repeated instructions regarding HBP measurement to the patients or the use of stored BP measurements is recommended to ensure accurate HBP measurements in patients with type 2 diabetes.

Pubmed
Journal: Nihon rinsho. Japanese journal of clinical medicine
January/13/1998
Pubmed
Journal: Nihon rinsho. Japanese journal of clinical medicine
January/13/1998
Authors
Pubmed
Journal: Health communication
April/19/2015
Abstract

The common comparison of depression to diabetes enables the construction of depression as a nonstigmatizing chronic illness that requires medication. We explore, through the use of discourse analysis, how both long-term users of antidepressants and family physicians invoked this analogy in research interviews. Specifically, we show how these participants explicitly or implicitly challenged the aptness of the depression-diabetes analogy as framed either within a generic (and presumably type 1) conception of diabetes or within the model of type 2 diabetes. These challenges include demonstrating how the elements or inferences of the analogy do not correspond, and how the analogy does not have its intended effects. We consider the implications of the unraveling of this analogy for the construction of depression as a chronic medical condition, for the supposed ease of prescribing and taking antidepressants, and for the reduction of stigma.

Pubmed
Journal: Lancet (London, England)
June/4/2008
Abstract

BACKGROUND

Delivery of high-quality, evidence-based health care to deprived sectors of the community is a major goal for society. We investigated the effectiveness of a culturally sensitive, enhanced care package in UK general practices for improvement of cardiovascular risk factors in patients of south Asian origin with type 2 diabetes.

METHODS

In this cluster randomised controlled trial, 21 inner-city practices in the UK were assigned by simple randomisation to intervention (enhanced care including additional time with practice nurse and support from a link worker and diabetes-specialist nurse [nine practices; n=868]) or control (standard care [12 practices; n=618]) groups. All adult patients of south Asian origin with type 2 diabetes were eligible. Prescribing algorithms with clearly defined targets were provided for all practices. Primary outcomes were changes in blood pressure, total cholesterol, and glycaemic control (haemoglobin A1c) after 2 years. Analysis was by intention to treat. This trial is registered, number ISRCTN 38297969.

RESULTS

We recorded significant differences between treatment groups in diastolic blood pressure (1.91 [95% CI -2.88 to -0.94] mm Hg, p=0.0001) and mean arterial pressure (1.36 [-2.49 to -0.23] mm Hg, p=0.0180), after adjustment for confounders and clustering. We noted no significant differences between groups for total cholesterol (0.03 [-0.04 to 0.11] mmol/L), systolic blood pressure (-0.33 [-2.41 to 1.75] mm Hg), or HbA1c (-0.15% [-0.33 to 0.03]). Economic analysis suggests that the nurse-led intervention was not cost effective (incremental cost-effectiveness ratio pound28 933 per QALY gained). Across the whole study population over the 2 years of the trial, systolic blood pressure, diastolic blood pressure, and cholesterol decreased significantly by 4.9 (95% CI 4.0-5.9) mm Hg, 3.8 (3.2-4.4) mm Hg, and 0.45 (0.40-0.51) mmol/L, respectively, and we recorded a small and non-significant increase for haemoglobin A1c (0.04% [-0.04 to 0.13]), p=0.290).

CONCLUSIONS

We recorded additional, although small, benefits from our culturally tailored care package that were greater than the secular changes achieved in the UK in recent years. Stricter targets in general practice and further measures to motivate patients are needed to achieve best possible health-care outcomes in south Asian patients with diabetes.

Pubmed
Journal: International journal of cardiology
November/1/2006
Abstract

Patients with diabetes mellitus have a much higher rate of cardiovascular disease (CVD) than the general population, and, in addition to glycaemia and hypertension, dyslipidemia has emerged as an important modifiable cardiovascular risk factor in these patients. In most patients with type 2 diabetes, the major features of dyslipidemia are increased triglyceride levels, decreased high-density lipoprotein cholesterol (HDL-C) levels, and changes in the composition and level of low-density lipoprotein cholesterol (LDL-C). Clinical trials evaluating both primary and secondary prevention of CVD demonstrate that lipid-lowering therapy results in a substantial reduction of cardiovascular risk in patients with type 2 diabetes. Low-density lipoprotein cholesterol is the first priority for treatment, with a statin in adequate dosage as the first choice for pharmacological therapy. The first statin trial conducted solely in patients with type 2 diabetes and no prior CVD demonstrated a 37% reduction in cardiovascular events in patients randomized to atorvastatin 10 mg compared with placebo. Additional trials that further address the benefits of lipid-lowering therapy in patients with diabetes are near completion, or are underway, and should provide important information about further attenuating risk in patients with diabetes.

Pubmed
Journal: Endocrinology and metabolism clinics of North America
November/2/2006
Abstract

Both type 1 and type 2 diabetes melitius are associated with increased cardiovascular morbidity, and now affect more than 170 million individuals worldwide. The incidence of type 2 diabetes is growing rapidly and now accounts for 90 to 95 percent of all diabetes cases. Thiazolidinediones (TZDs) a class of insulin sensitizing agents commonly used in the treatment of patients who have type 2 diabetes, improve endothelial dysfunction and exert beneficial effects on lipid profiles by activating the nuclear receptor peroxisome proliferator-activated receptor gamma (PPAR-gamma). In addition, TZDs exhibit antiatherogenic effects, independent of their antidiabetic and lipid-lowering properties, by attenuating proinflammatory processes. The combination of increased insulin sensitivity, improved lipid profile, and reduced inflammation may explain the cardiovascular benefits of this class of drugs

Pubmed
Journal: International journal of clinical practice
December/7/2008
Abstract

OBJECTIVE

The aim of this analysis was to assess the efficacy and safety of intensifying insulin therapy from a basal-only regimen to biphasic insulin aspart 30 (BIAsp 30) in patients with type 2 diabetes previously failing to reach glycaemic targets.

METHODS

The analysis is based on data from a subpopulation of the Physicians' Routine Evaluation of Safety and Efficacy of NovoMix 30 Therapy (PRESENT) study, which was a 6-month observational study in 15 countries. This subanalysis included patients previously receiving long-acting analogue insulin (AB; n = 348), or human basal insulin (long and intermediate acting) (HB; n = 3414), who were transferred to BIAsp 30. Efficacy end-points included change in glycated haemoglobin (HbA(1c)), fasting plasma glucose (FPG) and postprandial plasma glucose (PPG), from baseline to the end of the study. Episodes of hypoglycaemia, adverse events, and physician and patient satisfaction were also recorded. End-points were considered separately by previous basal regimen (AB or HB).

RESULTS

After 6 months' treatment with BIAsp 30, HbA(1c) was significantly lowered in both groups (-1.60% and -1.42% in the AB and HB groups; p < 0.0001 compared with baseline). Reductions in FPG and PPG were also statistically significant in both groups. The rate (events/patient/year) of overall hypoglycaemia remained relatively constant in patients switching from AB, but it was statistically lower in patients switching from HB (change from baseline -3.8; p < 0.001).

CONCLUSIONS

In routine clinical practice, patients with type 2 diabetes who are failing to reach glycaemic targets on basal insulin can achieve better glycaemic control without an increase in overall hypoglycaemia by intensifying with BIAsp 30.

Pubmed
Journal: Clinical journal of the American Society of Nephrology : CJASN
June/20/2016
Abstract

OBJECTIVE

Endothelin A receptor antagonists (ERAs) decrease residual albuminuria in patients with diabetic kidney disease; however, their clinical utility may be limited by fluid retention. Consequently, the primary objective of this study was to identify predictors for ERA-induced fluid retention among patients with type 2 diabetes and CKD. A secondary objective was to determine if the degree of fluid retention necessarily correlated with the magnitude of albuminuria reduction in those patients receiving ERAs.

METHODS

A post hoc analysis was conducted of the phase IIb atrasentan trials assessing albuminuria reduction in 211 patients with type 2 diabetes, urine albumin/creatinine ratios of 300-3500 mg/g, and eGFRs of 30-75 ml/min per 1.73 m(2) who were randomly assigned to receive placebo (n=50) or atrasentan 0.75 mg/d (n=78) or 1.25 mg/d (n=83) for 12 weeks. Changes in body weight and hemoglobin (Hb) after 2 weeks of treatment were used as surrogate markers of fluid retention.

RESULTS

Baseline predictors of weight gain after 2 weeks of atrasentan treatment were higher atrasentan dose, lower eGFR, higher glycated hemoglobin, higher systolic BP, and lower homeostatic metabolic assessment product. Higher atrasentan dose and lower eGFR also predicted decreases in Hb. There were no changes in B-type natriuretic peptide. There was no correlation between reduction in albuminuria after 2 weeks of atrasentan treatment and changes in body weight or Hb.

CONCLUSIONS

In the Reducing Residual Albuminuria in Subjects With Diabetes and Nephropathy With Atrasentan/JAPAN trials, atrasentan-associated fluid retention was more likely in patients with diabetes and nephropathy who had lower eGFR or received a higher dose of atrasentan. Finding that albuminuria reduction was not associated with changes in body weight and Hb suggests that the albuminuria-reducing efficacy of atrasentan is not impaired by fluid retention.

Pubmed
Journal: Inflammatory bowel diseases
May/30/2011
Abstract

BACKGROUND

Recent animal studies and clinical trials suggest that thiazolidinediones, a class of oral antidiabetic agents, are efficacious in reducing inflammation, yet no studies have evaluated their effectiveness in preventing flares. We examined the association between thiazolidinedione use and ulcerative colitis (UC)-related flares.

METHODS

We conducted a retrospective cohort study using administrative data from 87 health plans across 33 states. Individuals with both UC and diabetes were identified using administrative definitions. Exposure to thiazolidinediones or other oral antidiabetic agents was ascertained through outpatient pharmacy claims. The primary outcome was occurrence of a UC flare defined by: 1) a new prescription for oral steroids, infliximab, or oral/rectal salicylates, or 2) a claim for colectomy. Secondary analyses analyzed outcomes separately. We estimated hazard ratios (HRs) and 95% confidence intervals (CIs) using Cox proportional hazards regression after matching each thiazolidinedione user to a comparable oral antidiabetic user on propensity score.

RESULTS

This study included 142 thiazolidinedione and 468 other oral antidiabetic users with a mean follow-up of 7.3 and 6.2 months, respectively. Thiazolidinedione use was not associated with UC-related flares as measured by the composite outcome (HR = 1.05, 95% CI: 0.66, 1.68). However, thiazolidinedione use was associated with a nonsignificant reduction in risk of oral steroid use when analyzed as a separate outcome (HR = 0.53, 95% CI: 0.20, 1.44).

CONCLUSIONS

Thiazolidinediones do not provide any benefit over other oral antidiabetics in preventing UC-related flares as measured by our primary composite outcome. However, thiazolidinedione use may reduce the risk of more significant disease flares requiring oral steroid treatment.

Pubmed
Journal: The Journal of endocrinology
September/11/2011
Abstract

The inositol 1,4,5-trisphosphate receptors (IP3Rs) as ligand-gated Ca(2)(+) channels are key modulators of cellular processes. Despite advances in understanding their critical role in regulating neuronal function and cell death, how this family of proteins impact cell metabolism is just emerging. Unexpectedly, a transgenic mouse line (D2D) exhibited progressive glucose intolerance as a result of transgene insertion. Inverse PCR was used to identify the gene disruption in the D2D mice. This led to the discovery that Itpr1 is among the ten loci disrupted in chromosome 6. Itpr1 encodes for IP3R1, the most abundant IP3R isoform in mouse brain and also highly expressed in pancreatic β-cells. To study IP3R1 function in glucose metabolism, we used the Itpr1 heterozygous mutant mice, opt/+. Glucose homeostasis in male mice cohorts was examined by multiple approaches of metabolic phenotyping. Under regular diet, the opt/+ mice developed glucose intolerance but no insulin resistance. Decrease in second-phase glucose-stimulated blood insulin level was observed in opt/+ mice, accompanied by reduced β-cell mass and insulin content. Strikingly, when fed with high-fat diet, the opt/+ mice were more susceptible to the development of hyperglycemia, glucose intolerance, and insulin resistance. Collectively, our studies identify the gene Itpr1 being interrupted in the D2D mice and uncover a novel role of IP3R1 in regulation of in vivo glucose homeostasis and development of diet-induced diabetes.

Pubmed
Journal: BMC endocrine disorders
March/6/2016
Abstract

BACKGROUND

While poor sleep quality can worsen cardiovascular risk factors such as glucose and lipid profiles in patients with type 2 diabetes mellitus (T2DM), the relationship between sleep quality and atherosclerosis remains largely unknown. The aim of this study was to examine this relationship.

METHODS

The study participants comprised 724 Japanese T2DM outpatients free of history of cardiovascular diseases. The relationships between sleep quality (assessed by the Pittsburgh Sleep Quality Index (PSQI)) and various clinical and laboratory parameters were investigated.

RESULTS

The mean PSQI was 5.1 ± 3.0 (±SD). Patients were divided into three groups based on the total PSQI score; subjects with good sleep quality (n = 462), average sleep quality (n = 185), and poor sleep quality (n = 77). In the age/gender-adjusted model, patients with poor sleep quality tended to be obese, evening type and depressed. However, other lifestyles showed no significant trends. Alanine aminotransferase, fasting blood glucose, HbA1c, systolic blood pressure, urinary albumin excretion, and brachial-ankle pulse wave velocity (baPWV) tended to be higher in patients with poor sleep quality. High baPWV was the only parameter that correlated with poor sleep in a model adjusted for several other lifestyle factors.

CONCLUSIONS

Our study indicates that poor sleep quality in T2DM patients correlates with increased arterial wall stiffness, a marker of atherosclerosis and a risk factor for cardiovascular diseases.

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