Decreased insulin secretion and increased risk of type 2 diabetes associated with allelic variations of the WFS1 gene: the Data from Epidemiological Study on the Insulin Resistance Syndrome (DESIR) prospective study

A major reason for the increased incidence of type 2 diabetes mellitus (T2DM) across the world is the so-called obesity epidemic, which occurs both in developed and developing countries. However, a large proportion of patients with T2DM in European and, in particular, Asian countries are non-obese. The non-obese T2DM phenotype is characterized by disproportionally reduced insulin secretion and less insulin resistance, as compared with obese patients with T2DM. Importantly, non-obese patients with T2DM have a similar increased risk of cardiovascular disease as obese T2DM patients. The risk of T2DM in non-obese patients is influenced by genetics as well as factors operating in utero indicated by low birth weight. Furthermore, this phenotype is slightly more prevalent among patients with latent autoimmune diabetes in adults, characterized by positive anti-GAD antibodies. The recently identified TCF7L2 gene polymorphism resulting in low insulin secretion influences the risk of T2DM in both obese and non-obese subjects, but is relatively more prevalent among non-obese patients with T2DM. Furthermore, the Pro12Ala polymorphism of the PPARγ gene influencing insulin action increases the risk of T2DM in non-obese subjects. Despite a “normal” body mass index, non-obese patients with T2DM are generally characterized by a higher degree of both abdominal and total fat masses (adiposity). Prevention of T2DM with lifestyle intervention is at least as effective in non-obese as in obese prediabetic subjects, and recent data suggest that metformin treatment targeting insulin resistance and non-glycemic cardiovascular disease risk factors is as beneficial in non-obese as in obese patients with T2DM. Nevertheless, non-obese patients with T2DM may progress to insulin treatment more rapidly as compared with obese patients with T2DM.

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1516-P: A Comparison of the Contributions of Impaired Insulin Secretion and Insulin Resistance to the Development of Type 2 Diabetes in a Japanese Community: The Hisayama Study

Diabetes ◽

10.2337/db19-1516-p ◽

2019 ◽

Vol 68 (Supplement 1) ◽

pp. 1516-P

Author(s):

MASAHITO YOSHINARI ◽

YOICHIRO HIRAKAWA ◽

JUN HATA ◽

MAYU HIGASHIOKA ◽

TAKANORI HONDA ◽

...

Keyword(s):

Insulin Resistance ◽

Type 2 Diabetes ◽

Insulin Secretion ◽

Impaired Insulin Secretion ◽

Impaired Insulin

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Echinops Spp. Polysaccharide B Ameliorates Metabolic Abnormalities in a Rat Model of Type 2 Diabetes Mellitus

Current Topics in Nutraceutical Research ◽

10.37290/ctnr2641-452x.19:106-114 ◽

2020 ◽

Vol 19 (1) ◽

pp. 106-114

Author(s):

Guang Hao ◽

Xiaoyu Ma ◽

Mengru Jiang ◽

Zhenzhen Gao ◽

Ying Yang

Keyword(s):

Diabetes Mellitus ◽

Insulin Resistance ◽

Type 2 Diabetes ◽

Type 2 Diabetes Mellitus ◽

Insulin Secretion ◽

Insulin Receptor ◽

Skeletal Muscles ◽

Insulin Receptor Substrate ◽

Sprague Dawley

This study examined the in vivo effects of Echinops spp. polysaccharide B on type 2 diabetes mellitus in Sprague-Dawley rats. We constructed a type 2 diabetes mellitus Sprague-Dawley rat models by feeding a high-fat and high-sugar diet plus intraperitoneal injection of a small dose of streptozotocin. Using this diabetic rat model, different doses of Echinops polysaccharide B were administered orally for seven weeks. Groups receiving Xiaoke pill and metformin served as positive controls. The results showed that Echinops polysaccharide B treatment normalized the weight and blood sugar levels in the type 2 diabetes mellitus rats, increased muscle and liver glycogen content, improved glucose tolerance, increased insulin secretion, and reduced glucagon and insulin resistance indices. More importantly, Echinops polysaccharide B treatment upregulated the expression of insulin receptor in the liver, skeletal muscles, and pancreas, and significantly improved the expression levels of insulin receptor substrate-2 protein in the liver and pancreas, as well as it increased insulin receptor substrate-1 expression in skeletal muscles. These two proteins play crucial roles in increasing insulin secretion and in controlling type 2 diabetes mellitus. The findings of the present study suggest that Echinops polysaccharide B could improve the status of diabetes in type 2 diabetes mellitus rats, which may be achieved by improving insulin resistance. Our study provides a new insight into the development of a natural drug for the control of type 2 diabetes mellitus.

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TYK2 Promoter Variant, a Putative Virus-Induced Diabetes Susceptibility Gene, Is Associated with Impaired Insulin Secretion and Lower Insulin Resistance in Japanese Type 2 Diabetes Patients

SSRN Electronic Journal ◽

10.2139/ssrn.3667638 ◽

2020 ◽

Author(s):

Hitoe Mori ◽

Hirokazu Takahashi ◽

Keiichiro Mine ◽

Ken Higashimoto ◽

Kanako Inoue ◽

...

Keyword(s):

Insulin Resistance ◽

Type 2 Diabetes ◽

Insulin Secretion ◽

Susceptibility Gene ◽

Diabetes Susceptibility ◽

Impaired Insulin Secretion ◽

Diabetes Susceptibility Gene ◽

Impaired Insulin ◽

Diabetes Patients

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Visceral Adiposity Index is associated with Insulin Resistance, impaired Insulin Secretion, and β-cell dysfunction in subjects at risk for Type 2 Diabetes

Diabetes Epidemiology and Management ◽

10.1016/j.deman.2021.100013 ◽

2021 ◽

pp. 100013

Author(s):

Froylan David Martínez-Sánchez ◽

Valerie Paola Vargas-Abonce ◽

Andrea Rocha-Haro ◽

Romina Flores-Cardenas ◽

Milagros Fernández-Barrio ◽

...

Keyword(s):

Insulin Resistance ◽

Type 2 Diabetes ◽

At Risk ◽

Insulin Secretion ◽

Visceral Adiposity ◽

Visceral Adiposity Index ◽

Β Cell ◽

Cell Dysfunction ◽

Impaired Insulin

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Hyperinsulinemia and Its Pivotal Role in Aging, Obesity, Type 2 Diabetes, Cardiovascular Disease and Cancer

International Journal of Molecular Sciences ◽

10.3390/ijms22157797 ◽

2021 ◽

Vol 22 (15) ◽

pp. 7797

Author(s):

Joseph A. M. J. L. Janssen

Keyword(s):

Insulin Resistance ◽

Type 2 Diabetes ◽

Cardiovascular Disease ◽

Insulin Secretion ◽

Early Stage ◽

Insulin Clearance ◽

Future Research ◽

Age Related ◽

Hepatic Insulin Clearance

For many years, the dogma has been that insulin resistance precedes the development of hyperinsulinemia. However, recent data suggest a reverse order and place hyperinsulinemia mechanistically upstream of insulin resistance. Genetic background, consumption of the “modern” Western diet and over-nutrition may increase insulin secretion, decrease insulin pulses and/or reduce hepatic insulin clearance, thereby causing hyperinsulinemia. Hyperinsulinemia disturbs the balance of the insulin–GH–IGF axis and shifts the insulin : GH ratio towards insulin and away from GH. This insulin–GH shift promotes energy storage and lipid synthesis and hinders lipid breakdown, resulting in obesity due to higher fat accumulation and lower energy expenditure. Hyperinsulinemia is an important etiological factor in the development of metabolic syndrome, type 2 diabetes, cardiovascular disease, cancer and premature mortality. It has been further hypothesized that nutritionally driven insulin exposure controls the rate of mammalian aging. Interventions that normalize/reduce plasma insulin concentrations might play a key role in the prevention and treatment of age-related decline, obesity, type 2 diabetes, cardiovascular disease and cancer. Caloric restriction, increasing hepatic insulin clearance and maximizing insulin sensitivity are at present the three main strategies available for managing hyperinsulinemia. This may slow down age-related physiological decline and prevent age-related diseases. Drugs that reduce insulin (hyper) secretion, normalize pulsatile insulin secretion and/or increase hepatic insulin clearance may also have the potential to prevent or delay the progression of hyperinsulinemia-mediated diseases. Future research should focus on new strategies to minimize hyperinsulinemia at an early stage, aiming at successfully preventing and treating hyperinsulinemia-mediated diseases.

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Is Vitamin D Deficiency Related to Increased Cancer Risk in Patients with Type 2 Diabetes Mellitus?

International Journal of Molecular Sciences ◽

10.3390/ijms22126444 ◽

2021 ◽

Vol 22 (12) ◽

pp. 6444

Author(s):

Anna Gabryanczyk ◽

Sylwia Klimczak ◽

Izabela Szymczak-Pajor ◽

Agnieszka Śliwińska

Keyword(s):

Diabetes Mellitus ◽

Risk Factors ◽

Insulin Resistance ◽

Type 2 Diabetes ◽

Vitamin D ◽

Cancer Risk ◽

Vitamin D Deficiency ◽

Cancer Development ◽

Increased Risk

There is mounting evidence that type 2 diabetes mellitus (T2DM) is related with increased risk for the development of cancer. Apart from shared common risk factors typical for both diseases, diabetes driven factors including hyperinsulinemia, insulin resistance, hyperglycemia and low grade chronic inflammation are of great importance. Recently, vitamin D deficiency was reported to be associated with the pathogenesis of numerous diseases, including T2DM and cancer. However, little is known whether vitamin D deficiency may be responsible for elevated cancer risk development in T2DM patients. Therefore, the aim of the current review is to identify the molecular mechanisms by which vitamin D deficiency may contribute to cancer development in T2DM patients. Vitamin D via alleviation of insulin resistance, hyperglycemia, oxidative stress and inflammation reduces diabetes driven cancer risk factors. Moreover, vitamin D strengthens the DNA repair process, and regulates apoptosis and autophagy of cancer cells as well as signaling pathways involved in tumorigenesis i.e., tumor growth factor β (TGFβ), insulin-like growth factor (IGF) and Wnt-β-Cathenin. It should also be underlined that many types of cancer cells present alterations in vitamin D metabolism and action as a result of Vitamin D Receptor (VDR) and CYP27B1 expression dysregulation. Although, numerous studies revealed that adequate vitamin D concentration prevents or delays T2DM and cancer development, little is known how the vitamin affects cancer risk among T2DM patients. There is a pressing need for randomized clinical trials to clarify whether vitamin D deficiency may be a factor responsible for increased risk of cancer in T2DM patients, and whether the use of the vitamin by patients with diabetes and cancer may improve cancer prognosis and metabolic control of diabetes.

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