Familiality of metabolic abnormalities is dependent on age at onset and phenotype of the type 2 diabetic proband

2003 ◽  
Vol 285 (6) ◽  
pp. E1297-E1303 ◽  
Author(s):  
D. Tripathy ◽  
E. Lindholm ◽  
B. Isomaa ◽  
C. Saloranta ◽  
T. Tuomi ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Type 2 Diabetes ◽  
Insulin Secretion ◽  
Glucose Tolerance Test ◽  
Age At Onset ◽  
Tolerance Test ◽  
First Degree Relatives ◽  
History Of ◽  
The Common

To determine the impact of a family history of the common form of type 2 diabetes and the phenotype of the proband on anthropometric and metabolic variables in normoglycemic first-degree relatives, we studied 2,100 first-degree relatives of patients with the common form of type 2 diabetes (FH+) and 388 subjects without a family history of diabetes (FH–). All subjects participated in an oral glucose tolerance test to allow measurement of insulin secretion [30-min incremental insulin/glucose (I/G 30)] and insulin sensitivity [homeostasis model assessment (HOMA) of insulin resistance (IR)]. A subset participated in a euglycemic clamp ( n = 75) and an intravenous glucose tolerance test ( n = 300). To study the effect of a particular phenotype of the proband, insulin secretion and sensitivity were also compared between first-degree relatives of diabetic probands with high and low waist-to-hip ratio (WHR) and probands with early and late onset of diabetes. FH+ subjects were more insulin resistant, as seen from a higher HOMA-IR index ( P = 0.006) and a lower rate of insulin-stimulated glucose uptake ( P = 0.001) and had more features of the metabolic syndrome ( P = 0.02, P = 0.0002) compared with FH– subjects. Insulin secretion adjusted for insulin resistance (disposition index, DI) was also lower in the FH+ vs. FH– subjects ( P = 0.04). Relatives of diabetic probands with a high WHR had reduced insulin-mediated glucose uptake compared with relatives of probands with a low WHR ( P = 0.04). Relatives of diabetic patients with age at onset <44 yr had higher HOMA IR ( P < 0.005) and lower DI ( P < 0.005) than relatives of patients with age at onset >65 yr (highest quartile). We conclude that early age at onset of type 2 diabetes and abdominal obesity have a significant influence on the metabolic phenotype in the nondiabetic first-degree relative.

scholarly journals Statins Are Associated With Increased Insulin Resistance and Secretion

2021 ◽  
Author(s):  
Fahim Abbasi ◽  
Cindy Lamendola ◽  
Chelsea S. Harris ◽  
Vander Harris ◽  
Ming-Shian Tsai ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Type 2 Diabetes ◽  
Insulin Secretion ◽  
Glucose Tolerance Test ◽  
Tolerance Test ◽  
Oral Glucose ◽  
Atherosclerotic Cardiovascular Disease ◽  
Oral Glucose Tolerance ◽  
Median Increase

Objective: Statin treatment reduces the risk of atherosclerotic cardiovascular disease but is associated with a modest increased risk of type 2 diabetes, especially in those with insulin resistance or prediabetes. Our objective was to determine the physiological mechanism for the increased type 2 diabetes risk. Approach and Results: We conducted an open-label clinical trial of atorvastatin 40 mg daily in adults without known atherosclerotic cardiovascular disease or type 2 diabetes at baseline. The co-primary outcomes were changes at 10 weeks versus baseline in insulin resistance as assessed by steady-state plasma glucose during the insulin suppression test and insulin secretion as assessed by insulin secretion rate area under the curve (ISR AUC ) during the graded-glucose infusion test. Secondary outcomes included glucose and insulin, both fasting and during oral glucose tolerance test. Of 75 participants who enrolled, 71 completed the study (median age 61 years, 37% women, 65% non-Hispanic White, median body mass index, 27.8 kg/m 2 ). Atorvastatin reduced LDL (low-density lipoprotein)-cholesterol (median decrease 53%, P <0.001) but did not change body weight. Compared with baseline, atorvastatin increased insulin resistance (steady-state plasma glucose) by a median of 8% ( P =0.01) and insulin secretion (ISR AUC ) by a median of 9% ( P <0.001). There were small increases in oral glucose tolerance test glucose AUC (median increase, 0.05%; P =0.03) and fasting insulin (median increase, 7%; P =0.01). Conclusions: In individuals without type 2 diabetes, high-intensity atorvastatin for 10 weeks increases insulin resistance and insulin secretion. Over time, the risk of new-onset diabetes with statin use may increase in individuals who become more insulin resistant but are unable to maintain compensatory increases in insulin secretion. REGISTRATION: URL: https://www.clinicaltrials.gov ; Unique identifier: NCT02437084.

scholarly journals Assessment of insulin secretion from the oral glucose tolerance test in white patients with type 2 diabetes

Diabetes Care ◽  
2000 ◽  
Vol 23 (9) ◽  
pp. 1440-1441 ◽  
Author(s):  
M. Stumvoll ◽  
A. Mitrakou ◽  
W. Pimenta ◽  
T. Jenssen ◽  
H. Yki-Jarvinen ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Insulin Secretion ◽  
Glucose Tolerance ◽  
Oral Glucose Tolerance Test ◽  
Glucose Tolerance Test ◽  
Tolerance Test ◽  
Oral Glucose ◽  
Oral Glucose Tolerance ◽  
White Patients

scholarly journals Clinical polymorphism of type 2 diabetes in children — the first study in Russia

2015 ◽  
Vol 61 (6) ◽  
pp. 10-16
Author(s):  
Irina Aleksandrovna Eremina ◽  
Tamara Leonidovna Kuraeva ◽  
Lubov Iosifovna Zilberman ◽  
Alexander Yur'evich Mayorov ◽  
Ekaterina Olegovna Koksharova
Keyword(s):  
Diabetes Mellitus ◽  
Type 2 Diabetes ◽  
Glucose Tolerance Test ◽  
Tolerance Test ◽  
Oral Glucose ◽  
Oral Glucose Tolerance ◽  
C Peptide ◽  
History Of ◽  
Peptide Secretion

Objective.To elucidate the specific features of diagnostics, clinical course and manifestations of type 2 diabetes mellitus (DM2) in the children of the Russian population.Material and methods.A total of 80 children presenting with DM2 were enrolled in the study including 70 available for the dynamic examination, with the follow-up period of 2.6 years (1.5; 4.5). The general clinical examination of the patients was supplemented by measuring insulin secretion, studying HLA-polymorphism of the DQ and DR-genes, and determination of type 1 diabetes (DM1) — related specific antibodies (At).Results.The median age at diagnosis of DM2 was 13 years (11.5; 15.5). 58.8% of the children had a family history of DM2 but only 26.3% of them had classical complaints of diabetes mellitus. In 65% of the children, DM2 was diagnosed when they were passing medical examination in connection with obesity (in 51.9% with the use the oral glucose tolerance test (OGTP); 48.1% of these children had the fasting blood glucose level above 7.0 mmol/l. Ketonuria at the onset of the disease was documented in 21.3% of the patients while 85% were either obese or overweight. Antibodies (ICA and IAA) were detected in 15.2% of the children at a low titer. The HLA-genotype associated with a high risk of development of DM1 was identified in 5.5% of the cases. The glycosylated hemoglobin test revealed its mean level of 7.1% (6.3; 8.5%) at the onset of diabetes; in the majority of the children, it fell down below 6.5% within the first 3 years of the disease. During this period, insulin and C-peptide secretion remained elevated. Insulin resistance was initially documented in 81.3% of the children; the dynamic observation failed to show its appreciable decrease. Insulin therapy initiated at the onset of the disease was prescribed to 30% of the patients. After 3 years, only 8% of the children retaining endogenous insulin secretion continued to use insulin.Conclusion.The asymptomatic onset of type 2 diabetes mellitus in the children and adolescents emphasizes the importance of its active diagnostics during the pubertal period in the high risk groups comprising the patients with obesity and the family history of DM2. In one third of the children, the diagnosis of DM2 was possible only with the use the oral glucose tolerance test. DM2 in the children and adolescents is characterized by clinical polymorphism in the form of acute manifestations in 21% of the cases and the absence of obesity and insulin resistance in 15 and 18% respectively. This finding suggests the necessity of differential diagnostics of such cases from DM1 and MODY. Rather high insulin and C-peptide secretion persists for 3 years after the onset of DM2 in the children. Therefore, they do not need insulin therapy during this period. The presence of ICA and IAA antibodies at low titers does not compromise diagnosis of DM2.

scholarly journals Reduced Birth Weight, Decreased Early-Phase Insulin Secretion, and Increased Glucose Concentrations after Oral Glucose Tolerance Test in Japanese Women Aged 20 Years with Family History of Type 2 Diabetes

2020 ◽  
Vol 2020 ◽  
pp. 1-6
Author(s):  
Mari Honda ◽  
Ayaka Tsuboi ◽  
Satomi Minato-Inokawa ◽  
Kaori Kitaoka ◽  
Mika Takeuchi ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Insulin Secretion ◽  
Birth Weight ◽  
Early Phase ◽  
Tolerance Test ◽  
Japanese Women ◽  
Oral Glucose ◽  
Model Assessment ◽  
History Of

Introduction. We tested the hypothesis that family history of type 2 diabetes (FHD) is associated with reduced birth weight and reduced insulin secretion later in life. Materials and Methods. Birth weight, body composition by whole-body dual-energy X-ray absorptiometry, and homeostasis model assessment-insulin resistance were compared between Japanese women aged 20 years with positive ( n = 73 ) and negative ( n = 258 ) FHD. A subsample of 153 women (57 with positive FHD) underwent a 75 g oral glucose tolerance test. Multivariate logistic regression analyses were used to identify the most important determinants of FHD. Results. Women with positive as compared with negative FHD had lower birth weight ( 3132 ± 364 vs. 3238 ± 418   g , p = 0.04 ). However, the current fat mass index and trunk/leg fat ratio, sophisticated measures of general and abdominal fat accumulation, respectively, did not differ. Women with positive FHD had a lower insulinogenic index ( 2.4 ± 7.3 vs. 6.2 ± 16 , p = 0.007 ) and higher area under the glucose curve ( 217 ± 47 vs. 198 ± 36   mg /dL/2 h, p = 0.006 ). However, fasting and postload insulinemia, homeostasis model assessment-insulin resistance, and Matsuda index did not differ. In multivariate logistic regression analysis, birth weight was marginally associated with FHD (odds ratio, 0.999; 95% confidential interval, 0.98-1.00000; p = 0.0509 ). Conclusions. FHD was associated not only with reduced birth weight but also with decreased early-phase insulin secretion and increased postload glucose concentrations in Japanese women aged 20 years. These findings may be in keeping with the fetal insulin hypothesis and provide some evidence that FHD can alter size at birth, probably through genetic and shared environmental components, which consequently resulted in decreased early-phase insulin secretion and increased glucose excursion in the early twenties. FHD was not related to sophisticated measures of general and abdominal adiposity and insulin resistance/sensitivity.

Progression of Prediabetes to Type 2 Diabetes Mellitus in Thai Population

2021 ◽  
Vol 104 (5) ◽  
pp. 772-780
Keyword(s):  
Diabetes Mellitus ◽  
Type 2 Diabetes ◽  
Type 2 Diabetes Mellitus ◽  
Family History ◽  
Glucose Tolerance Test ◽  
Tolerance Test ◽  
Thai Population ◽  
History Of

Background: Pre-diabetes (pre-DM) increases the risk of developing type 2 diabetes mellitus (T2DM). The incidence of progression from pre-DM to T2DM varies in different ethnic populations. Objective: To examine the rate of progression from pre-DM to T2DM in a Thai population. Materials and Methods: This was a cohort study involving participants with pre-DM, diagnosed according to the results of fasting plasma glucose (FPG) and plasma glucose levels two hours after a 75-g oral glucose tolerance test (OGTT) (2-h PG), including IFG+/IGT–, defined by an FPG of 100 to 125 mg/dL (IFG+) and a normal 2-h PG of less than 140 mg/dL (IGT–); IFG–/IGT+, defined by a normal FPG of less than 100 mg/dL (IFG–) and a 2-h PG of 140 to 199 mg/dL (IGT+), and IFG+/IGT+. Each participant was followed-up until diabetes developed or for three years. The incidence of progression to T2DM was calculated every year until the 3-year follow-up period. Results: Three hundred twenty-five pre-DM participants were enrolled and classified into the following categories: IFG+/IGT– (22.5%), IFG–/IGT+ (44.3%), and IFG+/IGT+ (33.2%). During the 3-year follow-up period, 63 of 325 (19.4%) participants developed T2DM. The incidence of progression to T2DM was 3.1%, 5.7%, and 11.8% at 1, 2, and 3 years, respectively. The mean time to progression to T2DM was 25.5 months. When comparing between subgroups of pre-DM, the IFG–/IGT+ or IFG+/IGT+ subgroups had a higher chance of developing T2DM than the IFG+/IGT– subgroup (p<0.05). Some risk factors, which were a family history of T2DM in first-degree relatives, FPG of 110 mg/dL or more, and an HbA1C of 6.0% or greater were significantly associated with the progression of T2DM in univariate analysis (p<0.05). However moderate-intensity exercise and diabetes self-management education (DSME) attainment were the protective factors (p<0.05). Conclusion: Almost one-fifth of the participants with pre-DM progressed to T2DM within three years. The annual incidence of DM development was 3.1%, 5.7%, and 11.8% at 1, 2, and 3 years, respectively. People with FPG of 110 mg/dL or more, and an HbA1C of 6.0% or higher, or IGT or combined IGT&IFG should be screened for DM more frequently, using FPG and HbA1C, perhaps every three to six months, especially in those with a family history of T2DM in first-degree relatives. Otherwise, lifestyle modification should be strongly emphasized to prevent development of T2DM in these people. Keywords: Pre-diabetes, Glucose tolerance test, Diabetes mellitus

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