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  • 1
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    The Atrial Natriuretic Peptide Genetic Variant rs5068 Is Associated With a Favorable Cardiometabolic Phenotype in a Mediterranean Population
    American Diabetes Association ; 2013
    In:  Diabetes Care Vol. 36, No. 9 ( 2013-09-01), p. 2850-2856
    Details
    In: Diabetes Care, American Diabetes Association, Vol. 36, No. 9 ( 2013-09-01), p. 2850-2856
    Abstract: We hypothesized that the minor allele of the atrial natriuretic peptide (ANP) genetic variant rs5068 is associated with a favorable cardiometabolic phenotype in a general Mediterranean population. RESEARCH DESIGN AND METHODS We genotyped a random sample of the residents of Ventimiglia di Sicilia, Sicily, for rs5068. RESULTS Genotype frequencies of rs5068 are AA, 93.5%; AG, 6.4%; and GG, 0.1%. All subsequent analyses are AA versus AG+GG. After adjusting for age and sex, the minor G allele is associated with lower BMI (estimate [SE]: −1.7 kg/m2 [0.8] , P = 0.04). In the AG+GG group, males with HDL cholesterol levels & lt;40 mg/dL are less frequent (P = 0.05) and obesity tends to be less prevalent (P = 0.07). Importantly, the G allele is associated with a lower prevalence of metabolic syndrome (P = 0.02). After adjusting for BMI, the above associations were attenuated. Independently of age, sex, and BMI, the minor allele is also associated with lower systolic blood pressure (−6.0 mmHg [2.5], P = 0.02) and lower prevalence of hypertension (odds ratio 0.41 [95% CI 0.20–0.83] , P = 0.01). CONCLUSIONS The association between the minor allele of rs5068 and a favorable cardiometabolic phenotype that we previously reported in a U.S. population is now replicated in a Mediterranean population in which the G allele of rs5068 is associated with lower blood pressure, BMI, and prevalence of hypertension and metabolic syndrome. These findings may lead to a diagnostic strategy to assess cardiometabolic risk and lay the foundation for the future development of an ANP or ANP-like therapy for metabolic syndrome.
    Type of Medium: Online Resource
    ISSN: 0149-5992 , 1935-5548
    URL: Article
    DOI: 10.2337/dc12-2337
    Language: English
    Publisher: American Diabetes Association
    Publication Date: 2013
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  • 2
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    Correspondence Between the Adult Treatment Panel III Criteria for Metabolic Syndrome and Insulin Resistance
    American Diabetes Association ; 2006
    In:  Diabetes Care Vol. 29, No. 3 ( 2006-03-01), p. 668-672
    Details
    In: Diabetes Care, American Diabetes Association, Vol. 29, No. 3 ( 2006-03-01), p. 668-672
    Abstract: OBJECTIVE—The aim of the present study was to assess the diagnostic accuracy of the Adult Treatment Panel III (ATP-III) definition of the metabolic syndrome in identifying insulin-resistant individuals and to explore alternative approaches to improve identification of insulin-resistant individuals among asymptomatic adults from the general population. RESEARCH DESIGN AND METHODS—The sample consisted of 256 non-Hispanic white subjects without treated hypertension or diabetes, from the Rochester (Minnesota) Heart Family Study (123 men and 133 women; aged 20–60 years). Frequently sampled intravenous glucose tolerance tests were performed in all subjects. The reference standard for insulin resistance was determined by Bergman’s minimal model; insulin resistance was defined as an insulin sensitivity index & lt;2 × 10 min−1 · μU−1 · ml−1. Component metabolic syndrome measures included blood pressure determined by sphygmomanometer; fasting serum triglycerides, HDL cholesterol, and glucose concentrations determined enzymatically; and waist circumference determined by tape measure. RESULTS—By ATP-III criteria, the prevalence of metabolic syndrome was 15.6% (16.3% in men and 15.1% in women; P = 0.465). The presence of metabolic syndrome had low sensitivity to identify insulin resistance (45% in men and 39% in women; sex difference, P = 0.137) but high specificity (93% in men and 95% in women; sex difference, P = 0.345). Based on the area under the receiver operating characteristic curve (AUC) constructed by counting metabolic syndrome components as recommended by ATP-III, diagnostic accuracy was fair (AUC = 0.797 in men and 0.747 in women). When component metabolic syndrome measures were considered as quantitative traits rather than dichotomized, use of waist circumference alone, rather than counting metabolic syndrome components, improved diagnostic accuracy for insulin resistance (in men, AUC = 0.906, P = 0.001; in women, AUC = 0.822, P = 0.10). CONCLUSIONS—Application of the ATP-III metabolic syndrome criteria provides good specificity but low sensitivity to screen asymptomatic white adults for insulin resistance. Measuring just waist circumference is simpler and may provide greater accuracy for identifying insulin resistance.
    Type of Medium: Online Resource
    ISSN: 0149-5992 , 1935-5548
    URL: Article
    DOI: 10.2337/diacare.29.03.06.dc05-0970
    Language: English
    Publisher: American Diabetes Association
    Publication Date: 2006
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  • 3
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    TCF7L2 Genotype and α -Cell Function in Humans Without Diabetes
    American Diabetes Association ; 2016
    In:  Diabetes Vol. 65, No. 2 ( 2016-02-01), p. 371-380
    Details
    In: Diabetes, American Diabetes Association, Vol. 65, No. 2 ( 2016-02-01), p. 371-380
    Abstract: The diabetes-associated allele in TCF7L2 increases the rate of conversion to diabetes; however, the mechanism by which this occurs remains elusive. We hypothesized that the diabetes-associated allele in this locus (rs7903146) impairs insulin secretion and that this defect would be exacerbated by acute free fatty acid (FFA)–induced insulin resistance. We studied 120 individuals of whom one-half were homozygous for the diabetes-associated allele TT at rs7903146 and one-half were homozygous for the protective allele CC. After a screening examination during which glucose tolerance status was determined, subjects were studied on two occasions in random order while undergoing an oral challenge. During one study day, FFA was elevated by infusion of Intralipid plus heparin. On the other study day, subjects received the same amount of glycerol as present in the Intralipid infusion. β-Cell responsivity indices were estimated with the oral C-peptide minimal model. We report that β-cell responsivity was slightly impaired in the TT genotype group. Moreover, the hyperbolic relationship between insulin secretion and β-cell responsivity differed significantly between genotypes. Subjects also exhibited impaired suppression of glucagon after an oral challenge. These data imply that a genetic variant harbored within the TCF7L2 locus impairs glucose tolerance through effects on glucagon as well as on insulin secretion.
    Type of Medium: Online Resource
    ISSN: 0012-1797 , 1939-327X
    URL: Article
    DOI: 10.2337/db15-1233
    Language: English
    Publisher: American Diabetes Association
    Publication Date: 2016
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  • 4
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    1476-P: Progression to Type 2 Diabetes from Normal or Impaired Fasting Glucose
    American Diabetes Association ; 2020
    In:  Diabetes Vol. 69, No. Supplement_1 ( 2020-06-01)
    Details
    In: Diabetes, American Diabetes Association, Vol. 69, No. Supplement_1 ( 2020-06-01)
    Abstract: The interaction of anthropometric variables with fasting blood glucose on progression from normal fasting glucose to overt diabetes (DM), is uncertain. In the Rochester Epidemiology Project (MN, USA), we identified 44,992 individuals with ≥ 2 fasting plasma glucose (FPG) tests from 2005-17, after excluding people who met criteria for DM (FPG & gt; 125mg/dL) on/before their first FPG. The cohort was 58% female, had an age range of 18-65 yrs (44 ± 10, Mean ± SD) and BMI of 29 ± 7 kg/m2. Subjects who did not develop DM were censored at their last FPG value on/before Dec 31, 2017. Those who developed DM were assigned an event date as the first diagnostic value. Over a median follow-up of 7 yrs, 3888 (8.6%) developed DM. The Kaplan-Meier 10-year cumulative risk of incident DM was 12.8% (CI 12.4%-13.3%). As expected, multivariable Cox modeling identified elevated initial FPG [100-109mg/dL (HR 2.0; 1.9-2.2); 110-125mg/dL (HR 5.8; 5.4-6.3)] as conferring increased risk. Other independent risks were male sex (HR 1.30; 95% CI 1.22-1.38) and abnormal BMI [ & lt;18 kg/m2 (2.67; 1.96-3.63), 25-29.9 kg/m2 (1.37; 1.23-1.52), 30-34.9 kg/m2 (2.15; 1.92-2.39), ≥ 35 kg/m2 (3.59; 3.23-3.99)]. A very strong, nonlinear, age effect was also noted, with a fitted hazard ratio for age 60 versus 20 of 2.65. In this large cohort, male sex, age and abnormal category of BMI (including underweight) are associated with increased risk of progression to DM and additive to baseline FPG. Disclosure A.M. Egan: None. C. Wood-Wentz: None. K.R. Bailey: None. A. Vella: Advisory Panel; Self; vTv Therapeutics, Zealand Pharma A/S. Research Support; Self; Novo Nordisk A/S, Xeris Pharmaceuticals, Inc.
    Type of Medium: Online Resource
    ISSN: 0012-1797 , 1939-327X
    URL: Article
    DOI: 10.2337/db20-1476-P
    Language: English
    Publisher: American Diabetes Association
    Publication Date: 2020
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  • 5
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    Relative Risk of Mortality Associated With Diabetes as a Function of Birth Weight
    American Diabetes Association ; 2005
    In:  Diabetes Care Vol. 28, No. 12 ( 2005-12-01), p. 2839-2843
    Details
    In: Diabetes Care, American Diabetes Association, Vol. 28, No. 12 ( 2005-12-01), p. 2839-2843
    Abstract: OBJECTIVE—Birth weight is a risk factor for both diabetes and mortality. Diabetes is a risk factor for mortality. Whether the excess mortality observed for diabetes varies with birth weight is unclear. RESEARCH DESIGN AND METHODS—Among all 2,508 Rochester, Minnesota, residents who first met research criteria for adult-onset diabetes in 1960–1995, 171 were born locally in-hospital after 1922 (i.e., birth weights available) as singleton, term infants. Each case subject and two age- and sex-matched nondiabetic control subjects (born locally, residing locally when the case subject met the criteria for diabetes) were followed through 31 December 2000 for vital status. RESULTS—Of the diabetic case subjects, 16% (27 of 171) died vs. 7% (25 of 342) of control subjects (P = 0.004). The difference was less for normal-birth-weight (NBW) (2,948– & lt;3,856 g) individuals (12% [12 of 102] vs. 8% [20 of 246] , P = 0.31) than for abnormal-birth-weight individuals (low birth weight [LBW] 20% [8 of 39] vs. 2% [1 of 46], P = 0.01; high birth weight [HBW] 23% [7 of 30] vs. 8% [4 of 50] , P = 0.16), as confirmed with age- and sex-adjusted Cox proportional hazards (diabetes-associated hazard ratio 1.4 [95% CI 0.69–2.90] for NBW vs. 4.8 [1.7–13.3] for abnormal birth weight, test for interaction P = 0.056). The observed diabetes deaths were greater than expected, based on mortality for the general population (27 vs. 13.3, P & lt; 0.001), with 70% of excess deaths occurring among LBW (8 vs. 2.2, P & lt; 0.001) and HBW (7 vs. 3.1, P = 0.03) individuals. CONCLUSIONS—The excess mortality observed for diabetes appears disproportionately concentrated among abnormal-birth-weight individuals, thus identifying a subset of at-risk diabetic individuals and reinforcing the importance of NBW deliveries.
    Type of Medium: Online Resource
    ISSN: 0149-5992 , 1935-5548
    URL: Article
    DOI: 10.2337/diacare.28.12.2839
    Language: English
    Publisher: American Diabetes Association
    Publication Date: 2005
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  • 6
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    71-OR: County Social Vulnerability and Disparities in Incidence of Diagnosed Diabetes
    American Diabetes Association ; 2022
    In:  Diabetes Vol. 71, No. Supplement_1 ( 2022-06-01)
    Details
    In: Diabetes, American Diabetes Association, Vol. 71, No. Supplement_1 ( 2022-06-01)
    Abstract: Individual sociodemographic factors determine risk of diabetes. However, the association of a multidimensional social vulnerability index (SVI) and incident diabetes is unknown. We used CDC data on incidence of diagnosed diabetes, 2011-2018, in adults ≥20 years and defined county social vulnerability using two CDC indices: SVI minority health (SVI-MH; includes 6 dimensions) and SVI (includes 4 dimensions) . Trends in the annual age-adjusted incident diabetes rate per 1000 adults (AADR) were derived from weighted least squares regression. Year and SVI-MH/SVI were fitted nonlinearly with spline functions to test 2018 vs. 20fold-changes in AADR for levels of SVI-MH/SVI. Expressed by SVI-MH percentiles, low (10th) , median (50th) , and high (90th) vulnerability corresponded to overall AADR of 6.8, 8.5, and 10.5, respectively. In all years, counties with higher vulnerability (ie, higher SVI-MH) had significantly higher AADR. In 2018, compared to 2011, counties with high vulnerability showed a small AADR fold-decrease (0.97 [0.95-0.98] ; P & lt;.001) . The AADR fold-decrease was larger in counties with median vulnerability (0.92 [0.90-0.94]; P & lt;.001) . In counties with low vulnerability, there was no AADR fold-change (P=.35) . Results for AADR analyzed by SVI were generally similar. In summary, US counties with high SVI-MH/SVI had high AADR, and these indices could inform multidimensional interventions for diabetes prevention. Disclosure K.R. Bailey: None. A. Vella: Advisory Panel; Crinetics Pharmaceuticals, Inc., Rezolute, Inc., vTv Therapeutics, Zealand Pharma A/S. Other Relationship; Novo Nordisk. M.M. Mielke: Consultant; Biogen, LabCorp. Funding National Institute on Minority Health and Health Disparities (NIH K23 MD016230)
    Type of Medium: Online Resource
    ISSN: 0012-1797
    URL: Article
    DOI: 10.2337/db22-71-OR
    Language: English
    Publisher: American Diabetes Association
    Publication Date: 2022
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  • 7
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    1202-P: Disparities in Incidence of Diagnosed Diabetes in Rural United States, 2011–2018
    American Diabetes Association ; 2022
    In:  Diabetes Vol. 71, No. Supplement_1 ( 2022-06-01)
    Details
    In: Diabetes, American Diabetes Association, Vol. 71, No. Supplement_1 ( 2022-06-01)
    Abstract: US rural, compared to non-rural, populations have diabetes health disparities. However, it is unknown if there are rural disparities in incident diabetes. We used CDC data on incidence of diagnosed diabetes in adults aged ≥20 years, available for 97.5% of US counties (n=3145/3226) . Trends in the annual age-adjusted incident diabetes rate per 1000 adults (AADR) were assessed by weighted least squares regression. Year was fitted nonlinearly with a spline function, and AADR fold-change was tested by a model-based contrast of 20vs. 2018. The average AADR of 8.7 (95% CI 8.6-8.7) ranged from 9.3 (in 2011) to 8.3 (in 2013) and 8.9 (in 2018) , and concealed subnational disparities based on rurality (Figure) . In 2018, compared with 2011, the AADR decreased for large central metro counties (most urban) with AADR fold-change of 0.92 (0.91-0.93) but increased for noncore counties (most rural) with AADR fold-change of 1. (1.01-1.08) (both P & lt;.01) . The AADR declined in counties with intermediate rurality except for micropolitan counties (no change; P=.56) . When stratified by region, the largest rural disparity in AADR was observed in the South, with smaller disparities in other regions. In summary, from 2011-2018, rural counties had the highest overall AADR. The overall disparity in trends based on county rurality and the disparity in incidence in the rural South and rural West highlight areas for diabetes primary prevention interventions. Disclosure K.R. Bailey: None. M.M. Mielke: Consultant; Biogen, LabCorp. A. Vella: Advisory Panel; Crinetics Pharmaceuticals, Inc., Rezolute, Inc., vTv Therapeutics, Zealand Pharma A/S. Other Relationship; Novo Nordisk. Funding National Institute on Minority Health and Health Disparities (NIH K23 MD016230)
    Type of Medium: Online Resource
    ISSN: 0012-1797
    URL: Article
    DOI: 10.2337/db22-1202-P
    Language: English
    Publisher: American Diabetes Association
    Publication Date: 2022
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  • 8
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    1006-P: Progression to Type 2 Diabetes Despite a Baseline Fasting Plasma Glucose ≤ 80 mg/dl in a Population-Based Cohort
    American Diabetes Association ; 2021
    In:  Diabetes Vol. 70, No. Supplement_1 ( 2021-06-01)
    Details
    In: Diabetes, American Diabetes Association, Vol. 70, No. Supplement_1 ( 2021-06-01)
    Abstract: Fasting plasma glucose (FPG) concentration is a major predictor of a person’s risk of developing diabetes mellitus (DM). However, we sought to examine characteristics of individuals who develop DM despite a baseline FPG of ≤ 80mg/dL. The Rochester Epidemiology Project (REP) links the medical records of virtually all persons who have resided in Olmsted County, MN, USA between 1966 and present. Electronic laboratory data are available from 2005. Using REP, we identified individuals with ≥ 2 FPG tests from 2005-17, after excluding people who met criteria for DM on/before their first FPG. Those who developed DM (FPG & gt; 125mg/dL) were assigned an event date as the date of their first diagnostic value. Subjects who did not develop DM were censored at their last FPG value on/before Dec 31, 2017. The entire cohort consisted of 44,815 individuals, of whom 3689 (8.2%) developed DM. Although higher baseline FPG was strongly related to development of DM, 2315 had a baseline FPG of ≤ 80mg/dL with 130 (5.6%) developing DM. Within this subset, those who progressed were older at baseline (40 ± 11 vs. 36 ± 12 years, p & lt;0.02) and were more likely to be male (38 vs. 22%, p & lt;0.001). Those who progressed had no difference between BMI at baseline and time of diagnosis (28 ± 8 vs. 29 ± 8 kg/m2, p=0.07). Medical record review suggested that individuals who progressed had high medical complexity. Specifically, 28 (22%) were repeatedly exposed to high dose glucocorticoids during follow up, including 10 (8%) who received a solid organ transplant. Fifteen (12%) had a substance abuse disorder. Nineteen (15%) were treated with insulin at one year following diagnosis, four of whom were diagnosed with type 1 DM. Twenty nine (22%) had a first degree relative with DM. Additional longitudinal follow up revealed that 20 (15%) were deceased at a median time of 2.5 years following the DM diagnosis. While progression to DM in the context of a baseline FPG of ≤ 80mg/dL is uncommon, it typically occurs in the setting of significant medical comorbidity. Disclosure A. M. Egan: None. C. Wood-wentz: None. K. R. Bailey: None. A. Vella: Research Support; Self; Novo Nordisk. Funding National Institutes of Health (DK78646, DK116231, DK126206, K12HD065987)
    Type of Medium: Online Resource
    ISSN: 0012-1797 , 1939-327X
    URL: Article
    DOI: 10.2337/db21-1006-P
    Language: English
    Publisher: American Diabetes Association
    Publication Date: 2021
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  • 9
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    Association of Birth Weight and Type 2 Diabetes in Rochester, Minnesota
    American Diabetes Association ; 2004
    In:  Diabetes Care Vol. 27, No. 10 ( 2004-10-01), p. 2512-2513
    Details
    In: Diabetes Care, American Diabetes Association, Vol. 27, No. 10 ( 2004-10-01), p. 2512-2513
    Type of Medium: Online Resource
    ISSN: 0149-5992 , 1935-5548
    URL: Article
    DOI: 10.2337/diacare.27.10.2512
    Language: English
    Publisher: American Diabetes Association
    Publication Date: 2004
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