The molecular genetics of non‐insulin‐dependent diabetes mellitus

Groop, Leif

doi:10.1046/j.1365-2796.1997.99897000.x

Cited by 34 publications

(20 citation statements)

References 26 publications

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“…In this study, the prevalence of diabetes was 3.28 times as high in the siblings of diabetic probands than in the spouse control group, a finding similar to that observed in other Caucasian populations (28)(29)(30). By contrast, there was no familial aggregation of IGT in the OOA.…”

Section: Diabetes In the Amishsupporting

confidence: 88%

Diabetes in the Old Order Amish: characterization and heritability analysis of the Amish Family Diabetes Study.

et al. 2000

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A table elsewhere in this issue shows conventional and Système International (SI) units and conversion factors for many substances. Diabetes in the Old Order AmishCharacterization and heritability analysis of the Amish Family Diabetes Study O R I G I N A L A R T I C L EOBJECTIVE -The Old Order Amish (OOA) are a genetically well-defined closed Caucasian founder population. The Amish Family Diabetes Study was initiated to identify susceptibility genes for type 2 diabetes. This article describes the genetic epidemiology of type 2 diabetes and related traits in this unique population. RESEARCH DESIGN AND METHODS -The study cohort comprised Amish probands with diabetes who were diagnosed between 35 and 65 years of age and their extended adult family members. We recruited 953 adults who represented 45 multigenerational families. Phenotypic characterization included anthropometry, blood pressure, diabetes status, lipid profile, and leptin levels.RESULTS -The mean age of study participants was 46 years, and the mean BMI was 26.9 kg/m 2 . Subjects with type 2 diabetes were older, more obese, and had higher insulin levels. The prevalence of diabetes in the OOA was approximately half that of the Caucasian individuals who participated in the Third National Health and Nutrition Examination Survey (95% CI 0.23-0.84).The prevalence of diabetes in the siblings of the diabetic probands was 26.5% compared with a prevalence of 7.0% in spouses (λ s = 3.28, 95% CI 1.58-6.80). The heritability of diabetes-related quantitative traits was substantial (13-70% for obesity-related traits, 10-42% for glucose levels, and 11-24% for insulin levels during the oral glucose tolerance test; P = 0.01 to Ͻ0.0001).CONCLUSIONS -Type 2 diabetes in the Amish has similar phenotypic features to that of the overall Caucasian population, although the prevalence in the Amish community is lower than that of the Caucasian population. There is significant familial clustering of type 2 diabetes and related traits. This unique family collection will be an excellent resource for investigating the genetic underpinnings of type 2 diabetes. E p i d e m i o l o g y / H e a l t h S e r v i c e s / P s y c h o s o c i a l R e s e a r c h 596DIABETES CARE, VOLUME 23, NUMBER 5, MAY 2000Diabetes in the Amish assimilation into the surrounding dominant culture and are widely known for their oldfashioned social and technological practices and characteristic dress. They do not proselytize and do not allow outsiders to marry into the sect. They represent both a religious and a genetic isolate (6). There is a high degree of consanguinity in the Old Order Amish (OOA). Although first-cousin marriages are not permitted, on average, OOA married couples are more closely related than second cousins once removed but less related than second cousins (9). Other features of this population include low relocation rates, a relatively high standard of living, large family sizes (average sibship size 6-7), and essentially complete genealogies dating back to the early 1700s (12-14 generatio...

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Section: Diabetes In the Amishsupporting

confidence: 88%

Diabetes in the Old Order Amish: characterization and heritability analysis of the Amish Family Diabetes Study.

et al. 2000

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“…Therefore, they are promising candidate genes for Type 2 diabetes [1,5,36]. To our knowledge there are no previous studies on the effects of common polymorphisms in genes regulating the proximal insulin signalling pathway in IGT subjects with regard to their conversion to Type 2 diabetes.…”

Section: Discussionmentioning

confidence: 99%

“…Type 2 diabetes mellitus is characterised by peripheral insulin resistance in liver, skeletal muscle and adipose tissue, as well as impaired insulin secretion [1]. Known major risk factors for the disease include obesity, central obesity, low physical activity, high intake of saturated fat and low intake of dietary fibre [2,3].…”

Section: Introductionmentioning

confidence: 99%

Common polymorphisms in the genes regulating the early insulin signalling pathway: effects on weight change and the conversion from impaired glucose tolerance to Type 2 diabetes.

Laukkanen

Pihlajamäki

Lindström³

et al. 2004

Diabetologia

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“…liver, skeletal muscle, adipose tissue, pancreatic β-cells) to insulin [1]. It has been well established that patients with diabetes mellitus, exhibit a high incidence of cardiac dysfunction and mortality [2].…”

Section: Introductionmentioning

confidence: 99%

Diabetes and mitochondrial oxidative stress: A study using heart mitochondria from the diabetic Goto-Kakizaki rat

Santos¹,

Palmeira²,

Seiça³

et al. 2003

Vascular Biochemistry

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Increasing evidence shows that the overproduction of reactive oxygen species, induced by diabetic hyperglycemia, contributes to the development of several cardiopathologies. The susceptibility of diabetic hearts to oxidative stress, induced in vitro by ADP-Fe 2+ in mitochondria, was studied in 12-month-old Goto-Kakizaki rats, a model of non-insulin dependent diabetes mellitus, and normal (non-diabetic) Wistar rats. In terms of lipid peroxidation the oxidative damage was evaluated on heart mitochondria by measuring both the O 2 consumption and the concentrations of thiobarbituric acid reactive substances. Diabetic rats display a more intense formation of thiobarbituric acid reactive substances and a higher O 2 consumption than nondiabetic rats. The oxidative damage, assessed by electron microscopy, was followed by an extensive effect on the volume of diabetic heart mitochondria, as compared with control heart mitochondria. An increase in the susceptibility of diabetic heart mitochondria to oxidative stress can be explained by reduced levels of endogenous antioxidants, so we proceeded in determining α-tocopherol, GSH and coenzyme Q content. Although no difference of α-tocopherol levels was found in diabetic rats as compared with control rat mitochondria, a significant reduction in GSH (21.5% reduction in diabetic rats) and coenzyme Q levels of diabetic rats was observed. The data suggest that a significant decrease of coenzyme Q 9 , a potent antioxidant involved in the elimination of mitochondria-generated reactive oxygen species, may be responsible for an increased susceptibility of diabetic heart mitochondria to oxidative damage. (Mol Cell Biochem 246: 163-170, 2003)

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The molecular genetics of non‐insulin‐dependent diabetes mellitus

Cited by 34 publications

References 26 publications

Diabetes in the Old Order Amish: characterization and heritability analysis of the Amish Family Diabetes Study.

Diabetes in the Old Order Amish: characterization and heritability analysis of the Amish Family Diabetes Study.

Common polymorphisms in the genes regulating the early insulin signalling pathway: effects on weight change and the conversion from impaired glucose tolerance to Type 2 diabetes.

Diabetes and mitochondrial oxidative stress: A study using heart mitochondria from the diabetic Goto-Kakizaki rat

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