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  • Online Resource  (8)
  • Carr, Darcy B.  (8)
  • Hull, Rebecca L.  (8)
  • 1
    Online Resource
    Online Resource
    Intra-Abdominal Fat Is a Major Determinant of the National Cholesterol Education Program Adult Treatment Panel III Criteria for the Metabolic Syndrome
    American Diabetes Association ; 2004
    In:  Diabetes Vol. 53, No. 8 ( 2004-08-01), p. 2087-2094
    Details
    In: Diabetes, American Diabetes Association, Vol. 53, No. 8 ( 2004-08-01), p. 2087-2094
    Abstract: The underlying pathophysiology of the metabolic syndrome is the subject of debate, with both insulin resistance and obesity considered as important factors. We evaluated the differential effects of insulin resistance and central body fat distribution in determining the metabolic syndrome as defined by the National Cholesterol Education Program (NCEP) Adult Treatment Panel III. In addition, we determined which NCEP criteria were associated with insulin resistance and central adiposity. The subjects, 218 healthy men (n = 89) and women (n = 129) with a broad range of age (26–75 years) and BMI (18.4–46.8 kg/m2), underwent quantification of the insulin sensitivity index (Si) and intra-abdominal fat (IAF) and subcutaneous fat (SCF) areas. The metabolic syndrome was present in 34 (15.6%) of subjects who had a lower Si [median: 3.13 vs. 6.09 × 10−5 min−1/(pmol/l)] and higher IAF (166.3 vs. 79.1 cm2) and SCF (285.1 vs. 179.8 cm2) areas compared with subjects without the syndrome (P & lt; 0.001). Multivariate models including Si, IAF, and SCF demonstrated that each parameter was associated with the syndrome. However, IAF was independently associated with all five of the metabolic syndrome criteria. In multivariable models containing the criteria as covariates, waist circumference and triglyceride levels were independently associated with Si and IAF and SCF areas (P & lt; 0.001). Although insulin resistance and central body fat are both associated with the metabolic syndrome, IAF is independently associated with all of the criteria, suggesting that it may have a pathophysiological role. Of the NCEP criteria, waist circumference and triglycerides may best identify insulin resistance and visceral adiposity in individuals with a fasting plasma glucose & lt;6.4 mmol/l.
    Type of Medium: Online Resource
    ISSN: 0012-1797 , 1939-327X
    URL: Article
    DOI: 10.2337/diabetes.53.8.2087
    Language: English
    Publisher: American Diabetes Association
    Publication Date: 2004
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  • 2
    Online Resource
    Online Resource
    Impact of Differences in Fasting Glucose and Glucose Tolerance on the Hyperbolic Relationship Between Insulin Sensitivity and Insulin Responses
    American Diabetes Association ; 2006
    In:  Diabetes Care Vol. 29, No. 2 ( 2006-02-01), p. 356-362
    Details
    In: Diabetes Care, American Diabetes Association, Vol. 29, No. 2 ( 2006-02-01), p. 356-362
    Abstract: OBJECTIVE—To determine whether the hyperbolic relationship between insulin sensitivity and the acute insulin response to glucose (AIRg) exists in subjects with impaired fasting glucose (IFG) or decreased glucose tolerance. RESEARCH DESIGN AND METHODS—We studied 219 healthy subjects (88 male and 131 female subjects, aged 26–75 years) with fasting plasma glucose (FPG) & lt;6.11 mmol/l. Subjects underwent an intravenous glucose tolerance test to determine the insulin sensitivity index (Si), AIRg, and the glucose disappearance constant (Kg), the latter a measure of intravenous glucose tolerance. RESULTS—Si and AIRg were inversely related for the entire cohort, and this relationship was not significantly different from hyperbolic. The inverse relationship between Si and AIRg was not significantly different when compared between groups based on fasting glucose (normal fasting glucose [NFG], FPG & lt;5.56 mmol/l vs. IFG, FPG 5.56–6.11 mmol/l) or by the Kg quartile. However, the curve relating Si and AIRg was left shifted in the IFG compared with NFG group (P & lt; 0.001) and was progressively more left shifted with decreasing Kg (P & lt; 0.001), consistent with decreasing β-cell function. These changes were not observed for the curves relating Si and fasting insulin, suggesting that in the fasting state β-cell function is maintained even in patients with mild IFG. Finally, the disposition index (DI) (Si × AIRg) was calculated as a measure of β-cell function. The DI progressively decreased with increasing FPG, even in the group of subjects classified as NFG. CONCLUSIONS—The inverse relationship between insulin sensitivity and AIRg is consistent with a hyperbola not only in subjects with normal glucose tolerance but also with mild IFG or decreased Kg. Based on a hyperbolic relationship, a decrease in β-cell function can be detected as FPG increases, even in patients who are normal glucose tolerant.
    Type of Medium: Online Resource
    ISSN: 0149-5992 , 1935-5548
    URL: Article
    DOI: 10.2337/diacare.29.02.06.dc05-1963
    Language: English
    Publisher: American Diabetes Association
    Publication Date: 2006
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  • 3
    Online Resource
    Online Resource
    Impact of Intra-Abdominal Fat and Age on Insulin Sensitivity and β-Cell Function
    American Diabetes Association ; 2004
    In:  Diabetes Vol. 53, No. 11 ( 2004-11-01), p. 2867-2872
    Details
    In: Diabetes, American Diabetes Association, Vol. 53, No. 11 ( 2004-11-01), p. 2867-2872
    Abstract: The prevalence of glucose intolerance and type 2 diabetes increases with age. To determine whether the hyperbolic relationship between insulin sensitivity and the insulin response is affected by age and whether the decline in β-cell function with age is related to increases in intra-abdominal fat or age per se, we studied 220 healthy subjects with fasting glucose & lt;6.1 mmol/l (89 men and 131 women, aged 26–75 years, BMI 18.7–40.4 kg/m2). The insulin sensitivity index (Si) and the acute insulin response to glucose (AIRg) were determined, and from these β-cell function was estimated as the disposition index (Si × AIRg). Intra-abdominal fat and subcutaneous fat areas were quantified by computed tomography. Si (5.40 ± 0.5 vs. 7.86 ± 0.7 ×10−5 min−1/[pmol/l]), P & lt; 0.01) was decreased and intra-abdominal fat (117 ± 10 vs. 81 ± 9 cm2, P & lt; 0.05) was increased in the oldest (age 60–75 years) versus the youngest (age 26–44 years) quartile. The hyperbolic relationship between Si and AIRg was present independent of age; thus, β-cell function measured as the disposition index (1,412 ± 120 vs. 2,125 ± 150 ×10−5 min−1, P & lt; 0.01) was lower in the oldest versus the youngest quartile. In multiple regression, intra-abdominal fat (r = −0.470, P & lt; 0.001) but not age was associated with Si, but both intra-abdominal fat (r = −0.198, P = 0.003) and age (r = −0.131, P = 0.05) were correlated with the disposition index. These data suggest that although intra-abdominal fat is a strong determinant of insulin sensitivity and β-cell function, age has an independent effect on β-cell function that may contribute to the increased prevalence of type 2 diabetes in older populations.
    Type of Medium: Online Resource
    ISSN: 0012-1797 , 1939-327X
    URL: Article
    DOI: 10.2337/diabetes.53.11.2867
    Language: English
    Publisher: American Diabetes Association
    Publication Date: 2004
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  • 4
    Online Resource
    Online Resource
    Gestational Diabetes Mellitus Increases the Risk of Cardiovascular Disease in Women With a Family History of Type 2 Diabetes
    American Diabetes Association ; 2006
    In:  Diabetes Care Vol. 29, No. 9 ( 2006-09-01), p. 2078-2083
    Details
    In: Diabetes Care, American Diabetes Association, Vol. 29, No. 9 ( 2006-09-01), p. 2078-2083
    Abstract: OBJECTIVE— We sought to determine whether a history of gestational diabetes mellitus (GDM) further increases the risk of cardiovascular disease (CVD) in parous women with first-degree relatives with type 2 diabetes. RESEARCH DESIGN AND METHODS— Women with (n = 332) and without (n = 663) a history of GDM were compared regarding 1) the revised National Cholesterol Education Program Adult Treatment Panel III metabolic syndrome criteria, 2) the prevalence of type 2 diabetes, and 3) self-reported CVD. RESULTS— Women with prior GDM were younger (48.6 ± 0.7 vs. 52.4 ± 0.6 years [means ± SE];P & lt; 0.001) and less likely to be postmenopausal (48.3 vs. 57.9%; P & lt; 0.005). Although both groups were obese (BMI 34.4 ± 1.2 vs. 33.7 ± 0.6 kg/m2), women with prior GDM were more likely to have metabolic syndrome (86.6 vs. 73.5%; P & lt; 0.001) and type 2 diabetes (93.4 vs. 63.3%; P & lt; 0.001). Moreover, they had a higher prevalence of CVD (15.5 vs. 12.4%; adjusted odds ratio 1.85 [95% CI 1.21–2.82];P = 0.005) that occurred at a younger age (45.5 ± 2.2 vs. 52.5 ± 1.9 years;P = 0.02) and was independent of metabolic syndrome (1.74 [1.10–2.76] ; P = 0.02) and type 2 diabetes (1.56 [1.002–2.43];P & lt; 0.05). CONCLUSIONS— Among women with a family history of type 2 diabetes, those with prior GDM were even more likely to not only have CVD risk factors, including metabolic syndrome and type 2 diabetes, but also to have experienced CVD events, which occurred at a younger age. Thus, women with both a family history of type 2 diabetes and personal history of GDM may be especially suitable for early interventions aimed at preventing or reducing their risk of CVD and diabetes.
    Type of Medium: Online Resource
    ISSN: 0149-5992 , 1935-5548
    URL: Article
    DOI: 10.2337/dc05-2482
    Language: English
    Publisher: American Diabetes Association
    Publication Date: 2006
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  • 5
    Online Resource
    Online Resource
    A Reduced-Fat Diet and Aerobic Exercise in J apanese A mericans With Impaired Glucose Tolerance Decreases Intra-Abdominal Fat and Improves Insulin Sensitivity but not β-Cell Function
    American Diabetes Association ; 2005
    In:  Diabetes Vol. 54, No. 2 ( 2005-02-01), p. 340-347
    Details
    In: Diabetes, American Diabetes Association, Vol. 54, No. 2 ( 2005-02-01), p. 340-347
    Abstract: Lifestyle modification reduces the risk of developing type 2 diabetes and may have its effect through improving insulin sensitivity, β-cell function, or both. To determine whether diet and exercise improve insulin sensitivity and/or β-cell function and to evaluate these effects over time, we quantified insulin sensitivity and the acute insulin response to glucose (AIRg) in 62 Japanese Americans (age 56.5 ± 1.3 years; mean ± SE) with impaired glucose tolerance (IGT) who were randomized to the American Heart Association (AHA) Step 2 diet plus endurance exercise (n = 30) versus the AHA Step 1 diet plus stretching (n = 32) for 24 months. β-Cell function (disposition index [DI]) was calculated as Si × AIRg, where Si is the insulin sensitivity index. The incremental area under the curve for glucose (incAUCg) was calculated from a 75-g oral glucose tolerance test. Intra-abdominal fat (IAF) and subcutaneous fat (SCF) areas were measured by computed tomography. At 24 months, the Step 2/endurance group had lower weight (63.1 ± 2.4 vs. 71.3 ± 2.9 kg; P = 0.004) and IAF (75.0 ± 7.9 vs. 112.7 ± 10.4 cm2; P = 0.03) and SCF (196.5 ± 18.0 vs. 227.7 ± 19.9 cm2; P & lt; 0.001) areas, greater Si (4.7 ± 0.5 vs. 3.3 ± 0.3 × 10−5 min · pmol−1 · l−1; P = 0.01), and a trend toward lower AIRg (294.9 ± 50.0 vs. 305.4 ± 30.0 pmol/l; P = 0.06) and incAUCg (8,217.3 ± 350.7 vs. 8,902.0 ± 367.2 mg · dl−1 · 2 h−1; P = 0.08) compared with the Step 1/stretching group after adjusting for baseline values. There was no difference in the DI (P = 0.7) between the groups. Si was associated with changes in weight (r = −0.426, P = 0.001) and IAF (r = −0.395, P = 0.003) and SCF (r = −0.341, P = 0.01) areas. Thus, the lifestyle modifications decreased weight and central adiposity and improved insulin sensitivity in Japanese Americans with IGT. However, such changes did not improve β-cell function, suggesting that this degree of lifestyle modifications may be limited in preventing type 2 diabetes over the long term.
    Type of Medium: Online Resource
    ISSN: 0012-1797 , 1939-327X
    URL: Article
    DOI: 10.2337/diabetes.54.2.340
    Language: English
    Publisher: American Diabetes Association
    Publication Date: 2005
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  • 6
    Online Resource
    Online Resource
    Long-Term Treatment With Rosiglitazone and Metformin Reduces the Extent of, but Does Not Prevent, Islet Amyloid Deposition in Mice Expressing the Gene for Human Islet Amyloid Polypeptide
    American Diabetes Association ; 2005
    In:  Diabetes Vol. 54, No. 7 ( 2005-07-01), p. 2235-2244
    Details
    In: Diabetes, American Diabetes Association, Vol. 54, No. 7 ( 2005-07-01), p. 2235-2244
    Abstract: Islet amyloid deposition in type 2 diabetes is associated with reduced β-cell mass. Therefore, interventions aimed at reducing islet amyloid formation may help preserve β-cell mass in type 2 diabetes. Rosiglitazone and metformin act by different mechanisms to improve insulin sensitivity and thereby reduce β-cell secretory demand, resulting in decreased release of insulin and islet amyloid polypeptide (IAPP), the unique constituent of islet amyloid deposits. We hypothesized that this reduced β-cell secretory demand would lead to reduced islet amyloid formation. Human IAPP (hIAPP) transgenic mice, a model of islet amyloid, were treated for 12 months with rosiglitazone (1.5 mg · kg−1 · day−1, n = 19), metformin (1 g · kg−1 · day−1, n = 18), or control (n = 17). At the end of the study, islet amyloid prevalence (percent islets containing amyloid) and severity (percent islet area occupied by amyloid), islet mass, β-cell mass, and insulin release were determined. Islet amyloid prevalence (44 ± 8, 13 ± 4, and 11 ± 3% for control, metformin-, and rosiglitazone-treated mice, respectively) and severity (9.2 ± 3.0, 0.22 ± 0.11, and 0.10 ± 0.05% for control, metformin-, and rosiglitazone-treated mice, respectively) were markedly reduced with both rosiglitazone (P & lt; 0.001 for both measures) and metformin treatment (P & lt; 0.001 for both measures). Both treatments were associated with reduced insulin release assessed as the acute insulin response to intravenous glucose (2,189 ± 857, 621 ± 256, and 14 ± 158 pmol/l for control, metformin-, and rosiglitazone-treated mice, respectively; P & lt; 0.05 for metformin vs. control and P & lt; 0.005 for rosiglitazone vs. control), consistent with reduced secretory demand. Similarly, islet mass (33.4 ± 7.0, 16.6 ± 3.6, and 12.2 ± 2.1 mg for control, metformin-, and rosiglitazone-treated mice, respectively) was not different with metformin treatment (P = 0.06 vs. control) but was significantly lower with rosiglitazone treatment (P & lt; 0.05 vs. control). When the decreased islet mass was accounted for, the islet amyloid–related decrease in β-cell mass (percent β-cell mass/islet mass) was ameliorated in both rosiglitazone- and metformin-treated animals (57.9 ± 3.1, 64.7 ± 1.4, and 66.1 ± 1.6% for control, metformin-, and rosiglitazone-treated mice, respectively; P & lt; 0.05 for metformin or rosiglitazone vs. control). In summary, rosiglitazone and metformin protect β-cells from the deleterious effects of islet amyloid, and this effect may contribute to the ability of these treatments to alleviate the progressive loss of β-cell mass and function in type 2 diabetes.
    Type of Medium: Online Resource
    ISSN: 0012-1797 , 1939-327X
    URL: Article
    DOI: 10.2337/diabetes.54.7.2235
    Language: English
    Publisher: American Diabetes Association
    Publication Date: 2005
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  • 7
    Online Resource
    Online Resource
    Progressive Loss of β-Cell Function Leads to Worsening Glucose Tolerance in First-Degree Relatives of Subjects With Type 2 Diabetes
    American Diabetes Association ; 2007
    In:  Diabetes Care Vol. 30, No. 3 ( 2007-03-01), p. 677-682
    Details
    In: Diabetes Care, American Diabetes Association, Vol. 30, No. 3 ( 2007-03-01), p. 677-682
    Abstract: OBJECTIVE—The relative roles of insulin resistance and β-cell dysfunction in the pathogenesis of impaired glucose tolerance (IGT) and type 2 diabetes are debated. First-degree relatives of individuals with type 2 diabetes are at increased risk of developing hyperglycemia. RESEARCH DESIGN AND METHODS—We evaluated the evolution of insulin sensitivity, β-cell function, glucose effectiveness, and glucose tolerance over 7 years in 33 nondiabetic, first-degree relatives of type 2 diabetic individuals using frequently sampled tolbutamide-modified intravenous and oral glucose tolerance tests. RESULTS—Subjects gained weight, and their waist circumference increased (P & lt; 0.05). Insulin sensitivity, the acute insulin response to glucose, and glucose effectiveness did not change significantly. However, when we accounted for the modulating effect of insulin sensitivity on insulin release, β-cell function determined as the disposition index decreased by 22% (P & lt; 0.05). This decrease was associated with declines in intravenous and oral glucose tolerance (P & lt; 0.05 and P & lt; 0.001, respectively). Of the subjects with normal glucose tolerance at the first assessment, we compared those who progressed to IGT with those who did not. The disposition index was 50% lower in the progressors than in the nonprogressors at follow-up (P & lt; 0.05). CONCLUSIONS—The decline in glucose tolerance over time in first-degree relatives of type 2 diabetic individuals is strongly related to the loss of β-cell function. Thus, early interventions to slow the decline in β-cell function should be considered in high-risk individuals.
    Type of Medium: Online Resource
    ISSN: 0149-5992 , 1935-5548
    URL: Article
    DOI: 10.2337/dc06-1834
    Language: English
    Publisher: American Diabetes Association
    Publication Date: 2007
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  • 8
    Online Resource
    Online Resource
    Genetic background determines the extent of islet amyloid formation in human islet amyloid polypeptide transgenic mice
    American Physiological Society ; 2005
    In:  American Journal of Physiology-Endocrinology and Metabolism Vol. 289, No. 4 ( 2005-10), p. E703-E709
    Details
    In: American Journal of Physiology-Endocrinology and Metabolism, American Physiological Society, Vol. 289, No. 4 ( 2005-10), p. E703-E709
    Abstract: Genetic background is important in determining susceptibility to metabolic abnormalities such as insulin resistance and β-cell dysfunction. Islet amyloid is associated with reduced β-cell mass and function and develops in the majority of our C57BL/6J × DBA/2J (F 1 ) male human islet amyloid polypeptide (hIAPP) transgenic mice after 1 yr of increased fat feeding. To determine the relative contribution of each parental strain, C57BL/6J (BL6) and DBA/2J (DBA2), to islet amyloid formation, we studied male hIAPP mice on each background strain (BL6, n = 13; and DBA2 n = 11) and C57BL/6J × DBA/2J F 1 mice ( n = 17) on a 9% (wt/wt) fat diet for 1 yr. At the end of 12 mo, islet amyloid deposition was quantified from thioflavin S-stained pancreas sections. The majority of mice in all groups developed islet amyloid (BL6: 91%, F 1 : 76%, DBA2: 100%). However, the prevalence (%amyloid-positive islets; BL6: 14 ± 3%, F 1 : 44 ± 8%, DBA2: 49 ± 9%, P 〈 0.05) and severity (%islet area occupied by amyloid; BL6: 0.03 ± 0.01%, F 1 : 9.2 ± 2.9%, DBA2: 5.7 ± 2.3%, p ≤ 0.01) were significantly lower in BL6 than F 1 and DBA2 mice. Increased islet amyloid severity was negatively correlated with insulin-positive area per islet, in F 1 ( r 2 = 0.75, P 〈 0.001) and DBA2 ( r 2 = 0.87, P 〈 0.001) mice but not BL6 mice ( r 2 = 0.07). In summary, the extent of islet amyloid formation in hIAPP transgenic mice is determined by background strain, with mice expressing DBA/2J genes (F 1 and DBA2 mice) being more susceptible to amyloid deposition that replaces β-cell mass. These findings underscore the importance of genetic and environmental factors in studying metabolic disease.
    Type of Medium: Online Resource
    ISSN: 0193-1849 , 1522-1555
    URL: Article
    DOI: 10.1152/ajpendo.00471.2004
    Language: English
    Publisher: American Physiological Society
    Publication Date: 2005
    detail.hit.zdb_id: 1477331-4
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