Familial clustering of arterial blood pressure, HDL cholesterol, and pro-insulin but not of insulin resistance and microalbuminuria in siblings of patients with type 2 diabetes.

Pontiroli, Antonio E.; Monti, Lucilla D.; Pizzini, Attilia Maria; Piatti, PierMarco

doi:10.2337/diacare.23.9.1359

Cited by 30 publications

(18 citation statements)

References 39 publications

(56 reference statements)

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“…[4][5][6][7][8][9] Similar findings have also been found in the offspring of individuals with type 2 DM, this mainly attributed to the increased risk of obesity, hyperinsulinemia and glucose intolerance. 7,[10][11][12] However, it is not yet clear whether a family history of DM per se is associated with dyslipidemia, or dyslipidemia is related to the obesity, hyperinsulinemia or glucose intolerance, usually present in subjects with family history of type 2 DM.…”

Section: Introductionsupporting

confidence: 68%

Low HDL-cholesterol among normal weight, normoglycemic offspring of individuals with type 2 diabetes mellitus

Praveen¹,

Kulshreshtha²,

Khurana³

et al. 2011

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ObjEctIvE: Offspring of type 2 diabetics have an increased risk of dyslipidemia, glucose intolerance and obesity. the aim of this study was to assess the lipid levels in the offspring of diabetics with normal glucose tolerance and normal body weight. DEsIGN: Normal weight offspring of patients with type 2 diabetes mellitus (DM) who had normal glucose tolerance, and healthy gender matched controls of comparable age without a family history of diabetes mellitus, were the subjects of this study. Lipid profiles were determined in cases and controls. rEsULts: the study included 114 subjects (64 males and 50 females) in each group, aged (mean±sD) 24.0±7.9 in cases and 24.1±8.0 years in controls. the body mass index (bMI) was 20.8±3.0 and 20.2±3.1 kg/m 2 in cases and controls, respectively. serum total cholesterol, triglycerides, plasma glucose, fasting insulin, c-peptide and proinsulin levels were comparable in cases and controls. serum high density lipoprotein (HDL) cholesterol was lower (p <0.001), whilst the serum triglyceride/HDL ratio, low density lipoprotein (LDL) cholesterol and area under the curve for insulin and proinsulin during an oral glucose tolerance test were higher in cases compared to controls. HDL cholesterol showed no significant correlation with plasma glucose, insulin or proinsulin. cONcLUsION: Plasma HDL cholesterol is low among normal weight, normoglycemic offspring of subjects with type 2 diabetes mellitus. the implications of this finding are not apparent.

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Section: Introductionsupporting

confidence: 68%

Low HDL-cholesterol among normal weight, normoglycemic offspring of individuals with type 2 diabetes mellitus

Praveen¹,

Kulshreshtha²,

Khurana³

et al. 2011

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“…Further, male and female first degree relatives of PCOS probands have been reported with elevated insulin levels (34). The significant correlations between PCOS probands and their sisters for glucose levels is consistent with a heritable component to this trait (35). One of the possible interpretations of the significant bimodal distribution of insulin levels among the sisters is that this may be a monogenic trait controlled by two alleles at an autosomal locus (13,30).…”

Section: Discussionmentioning

confidence: 51%

Insulin Resistance in the Sisters of Women with Polycystic Ovary Syndrome: Association with Hyperandrogenemia Rather Than Menstrual Irregularity

Legro

Bentley‐Lewis

Driscoll

et al. 2002

The Journal of Clinical Endocrinology & Metabolism

169

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This study was performed to determine whether the sisters of women with polycystic ovary syndrome (PCOS) have evidence for insulin resistance. Three hundred and thirty-six women with PCOS, 307 sisters of these probands, and 47 control women were studied. The sisters were grouped by phenotypes: PCOS [hyperandrogenemia (HA) with chronic oligo-or amenorrhea, n = 39], HA with regular menses (n = 36), unaffected (UA; n = 122), and unknown (n = 110). The analyses were adjusted for age and body mass index. PCOS and HA sisters of women with PCOS had similar and significantly elevated fasting insulin levels (P = 0.001) as well as similar and significantly decreased fasting glucose/insulin ratios (P < 0.001) suggestive of insulin resistance compared with UA sisters and control women. Markers of insulin resistance were associated with hyperandrogenemia and not with menstrual irregularity. PCOS sisters also had decreased levels of SHBG (P = 0.02) suggestive of higher ambient insulin levels. PCOS sisters had increased levels of proinsulin (P = 0.04) compared with control women, which suggested pancreatic β-cell dysfunction in this group of sisters. The magnitude of obesity also differed significantly among the groups of sisters. The PCOS sisters were significantly more obese than all the other groups, and the HA sisters were more obese than the UA sisters. We conclude that markers of insulin resistance are associated with hyperandrogenemia rather than menstrual irregularity in the sisters of women with PCOS. Menstrual irregularity may be related to the magnitude of insulin sensitivity or insulin secretion or to other factors associated with obesity.POLYCYSTIC OVARY syndrome (PCOS) is a disorder of unknown etiology characterized by chronic anovulation and hyperandrogenism (1). It remains a diagnosis of exclusion of Copyright © 2002 HHS Public Access Author ManuscriptAuthor Manuscript Author ManuscriptAuthor Manuscript specific disorders of the ovaries, adrenals, and pituitary gland. PCOS is frequently associated with insulin resistance (2). There is now convincing evidence from studies in which insulin levels have been lowered by several modalities that hyperinsulinemia contributes to the hyperandrogenemia (HA) and anovulation (3-7).Familial clustering of PCOS consistent with a genetic susceptibility to the disorder has been well documented (8)(9)(10)(11)(12). Recently, we have shown that there are two reproductive phenotypes in the sisters of women with PCOS: 1) chronic anovulation and HA consistent with typical PCOS, and 2) HA with regular menses and apparently normal fertility (13). Previous studies have suggested that women with HA and regular cycles were not insulin resistant (14-16). Family studies have suggested that HA in PCOS sisters is common and may be a monogenic trait (13,17). A twin study of PCOS women showed high correlation within twin pairs for both circulating androgen and fasting insulin levels (18). Defects in insulin action persist in cultured skin fibroblasts, and increased androgen productio...

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“…Previous evidence has shown that the offspring of individuals with type 2 diabetes have an increased risk of developing type 2 diabetes, with defects in early beta cell secretion [22][23][24][25]. It has also been suggested that these offspring have early autonomic dysfunction, even in the absence of glucose intolerance [26], and more often display metabolic abnormalities with high insulin levels and arterial hypertension [27,28]. In a previous community-based cohort, parental diabetes appeared to be an independent predictor of longitudinal changes in both systolic and diastolic BPs in the offspring, regardless of race and sex [29].…”

Section: Discussionmentioning

confidence: 99%

Parental history of type 2 diabetes, TCF7L2 variant and lower insulin secretion are associated with incident hypertension. Data from the DESIR and RISC cohorts

Bonnet¹,

Roussel

Natali³

et al. 2013

Diabetologia

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Aims/hypothesis The relationship between insulin secretion and the incidence of hypertension has not been well characterised. We hypothesised that both a parental history of diabetes and TCF7L2 rs7903146 polymorphism, which increases susceptibility to diabetes because of impaired beta cell function, are associated with incident hypertension. In a separate cohort, we assessed whether low insulin secretion is related to incident hypertension. Methods Nine year incident hypertension was studied in 2,391 normotensive participants from the Data from an Epidemiological Study on the Insulin Resistance Syndrome (DESIR) cohort. The relationship between insulin secretion and 3 year incident hypertension was investigated in 1,047 non-diabetic, normotensive individuals from the Relationship between Insulin Sensitivity and Cardiovascular Disease (RISC) cohort. Insulin secretion during OGTT was expressed in relation to the degree of insulin resistance, as assessed by a hyperinsulinaemic-euglycaemic clamp. Results In the DESIR cohort, a parental history of diabetes and the TCF7L2 at-risk variant were both associated with hypertension incidence at year 9, independently of waist circumference, BP, fasting glucose, insulin levels and HOMA-IR at inclusion (p=0.02 for parental history, p=0.006 for Members of the DESIR Study Group and the RISC investigators are listed in the electronic supplementary material (ESM).Electronic supplementary material The online version of this article (doi:10.1007/s00125-013-3021-y) contains peer-reviewed but unedited supplementary material, which is available to authorised users.

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Familial clustering of arterial blood pressure, HDL cholesterol, and pro-insulin but not of insulin resistance and microalbuminuria in siblings of patients with type 2 diabetes.

Cited by 30 publications

References 39 publications

Low HDL-cholesterol among normal weight, normoglycemic offspring of individuals with type 2 diabetes mellitus

Low HDL-cholesterol among normal weight, normoglycemic offspring of individuals with type 2 diabetes mellitus

Insulin Resistance in the Sisters of Women with Polycystic Ovary Syndrome: Association with Hyperandrogenemia Rather Than Menstrual Irregularity

Parental history of type 2 diabetes, TCF7L2 variant and lower insulin secretion are associated with incident hypertension. Data from the DESIR and RISC cohorts

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