Although overweight/obesity is a major risk factor for the development of type 2 diabetes mellitus, there is increasing evidence that overweight or obese patients with type 2 diabetes mellitus experience lower mortality compared with patients of normal weight. This paradoxical finding, known as the “obesity paradox,” occurs in other chronic diseases, and in type 2 diabetes mellitus is particularly perplexing given that lifestyle intervention with one goal being weight reduction is an important feature of the management of this condition. We summarize in this review the findings from clinical and epidemiologic studies that have investigated the association between overweight and obesity (usually assessed using body mass index [BMI]) and mortality in type 2 diabetes mellitus and discuss potential causes of the obesity paradox. We conclude that most studies show evidence of an obesity paradox, but important conflicting findings still exist. We also evaluate if potential bias might explain the obesity paradox in diabetes, including, for example, the presence of confounding factors, measurement error due to use of BMI as an index of obesity, and reverse causation.
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Multistate Models to Predict Development of Late Complications of Type 2 Diabetes in an Open Cohort Study
Is the Obesity Paradox in Type 2 Diabetes Due to Artefacts of Biases? An Analysis of Pooled Cohort Data from the Heinz Nixdorf Recall Study and the Study of Health in Pomerania
In cases of chronic hyperglycemia, advanced glycation end-products (AGEs) are actively produced and accumulated in the circulating blood and various tissues. AGEs also accelerate the expression of receptors for AGEs, and they play an important role in the development of diabetic vascular complications through various mechanisms. Active interventions for glucose and related risk factors may help improve the clinical course of patients by reducing AGEs. This review summarizes recent updates on AGEs that have a significant impact on diabetic vascular complications.
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Little is known about the natural course of normal fasting glucose (NFG) in Asians and the risk factors for future diabetes.
A total of 370 Japanese Americans (163 men, 207 women) with NFG levels and no history of diabetes, aged 34 to 75 years, were enrolled. Oral glucose tolerance tests were performed at baseline, 2.5, 5, and 10 years after enrollment.
During 10 years of follow-up, 16.1% of participants met criteria for diabetes diagnosis, and 39.6% of subjects still had NFG levels at the time of diabetes diagnosis. During 5 years of follow-up, age (odds ratio [OR], 1.05; 95% confidence interval [CI], 1.01 to 1.10;
A substantial number of subjects with NFG at baseline still remained in the NFG range at the time of diabetes diagnosis. A family history of diabetes and fasting insulin and glucose levels were associated with diabetes diagnosis during 10 years of follow-up; however, fasting glucose level was not associated with diabetes risk within the relatively short-term follow-up period of 5 years in subjects with NFG.
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Proprotein convertase subtilisin/kexin type 9 (PCSK9) is a circulating protein that promotes degradation of the low density lipoprotein receptor. PCSK9 has emerged as a target for lipid-lowering therapy, but the predictive value of the serum level of PCSK9 for the severity of coronary disease is largely unknown.
From December 2009 to July 2012, 121 individuals who underwent coronary angiography (CAG) because of clinically suspected acute coronary syndrome were enrolled in this study. Serum levels of PCSK9 and metabolic parameters were measured. SYNTAX (SYNergy between percutaneous coronary intervention with [paclitaxel-eluting] TAXUS stent and cardiac surgery) and GRACE (Global Registry of Acute Coronary Events) scores were calculated.
Individuals with CAG lesions (
Serum PCSK9 concentrations are higher in patients with coronary artery lesions, and are associated with SYNTAX and GRACE scores, suggesting that PCSK9 is a potential biomarker of the severity of coronary artery disease.
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The aim of this study was to investigate which glycemic parameters better reflect urinary N-acetyl-β-D-glucosaminidase (uNAG) abnormality, a marker for renal tubulopathy, in subjects with type 2 diabetes mellitus (T2DM) subjects with normoalbuminuria and a normal estimated glomerular filtration rate (eGFR).
We classified 1,061 participants with T2DM into two groups according to uNAG level—normal vs. high (>5.8 U/g creatinine)—and measured their biochemical parameters.
Subjects with high uNAG level had significantly higher levels of fasting and stimulated glucose, glycated albumin (GA), and glycosylated hemoglobin (HbA1c) and lower levels of homeostasis model assessment of β-cell compared with subjects with normal uNAG level. Multiple linear regression analyses showed that uNAG was significantly associated with GA (standardized β coefficient [β]=0.213,
GA is a more useful glycation index than HbA1c for reflecting renal tubulopathy in subjects with T2DM with normoalbuminuria and normal eGFR.
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To evaluate the prevalence of chronic kidney disease (CKD) and progression rate to CKD in elderly patients with type 2 diabetes mellitus (T2DM).
We investigated the medical records of 190 elderly patients (65 years or older) with T2DM from 2005 to 2011 in 6-month increments. Mean follow-up duration was 64.5 months. CKD was defined as estimated glomerular filtration rate (eGFR) <60 mL/min/1.73 m2 and/or the presence of albuminuria.
The mean age was 70.4 years and mean diabetes duration was 10.6 years. Among all the participants, 113 patients (59.5%) had CKD. The eGFR was significantly decreased between baseline (65.7±15.0 mL/min/1.73 m2) and the end of follow-up (52.7±17.5 mL/min/1.73 m2,
CKD was commonly observed in older patients with T2DM, and the progression rate to CKD is also high. Consequently, it is important to identify and manage CKD as early as possible in elderly patients with T2DM, especially in those with diabetes duration ≥10 years.
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Hepatic steatosis is caused by metabolic stress associated with a positive lipid balance, such as insulin resistance and obesity. Previously we have shown the anti-obesity effects of inhibiting serotonin synthesis, which eventually improved insulin sensitivity and hepatic steatosis. However, it is not clear whether serotonin has direct effect on hepatic lipid accumulation. Here, we showed the possibility of direct action of serotonin on hepatic steatosis.
Mice were treated with para-chlorophenylalanine (PCPA) or LP-533401 to inhibit serotonin synthesis and fed with high fat diet (HFD) or high carbohydrate diet (HCD) to induce hepatic steatosis. Hepatic triglyceride content and gene expression profiles were analyzed.
Pharmacological and genetic inhibition of serotonin synthesis reduced HFD-induced hepatic lipid accumulation. Furthermore, short-term PCPA treatment prevented HCD-induced hepatic steatosis without affecting glucose tolerance and browning of subcutaneous adipose tissue. Gene expression analysis revealed that the expressions of genes involved in
Short-term inhibition of serotonin synthesis prevented hepatic lipid accumulation without affecting systemic insulin sensitivity and energy expenditure, suggesting the direct steatogenic effect of serotonin in liver.
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Due to the multifactorial and multisystemic nature of diabetes mellitus, it is often treated with a combination of therapeutic agents having different mode of action. Earlier, we have synthesized several organozinc complexes and evaluated their safety and antidiabetic properties in experimental type 2 diabetes mellitus (T2DM). More recently, we have synthesized a metformin-3-hydroxyflavone complex and studied its antidiabetic efficacy in experimental rats. In the present study, a new zinc-mixed ligand (metformin-3-hydroxyflavone) was synthesized, characterized by spectral studies and its antidiabetic properties was evaluated in HFD fed—low dose streptozotocin induced T2DM in rats. The hypoglycemic efficacy of the complex was evaluated through oral glucose tolerance test, homeostasis model assessment of insulin resistance, quantitative insulin sensitivity check index and by determining the status of important biochemical parameters. Oral administration of the complex at a concentration of 10 mg/kg body weight/rat/day for 30 days significantly improved the glucose homeostasis. The complex possesses significant antidiabetic properties relatively at a less concentration than metformin-3-hydroxyflavone complex in ameliorating hyperglycemia.
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