Search

Lifestyle modification reduces the risk of developing type 2 diabetes and may have its effect through improving insulin sensitivity, beta-cell function, or both. To determine whether diet and exercise improve insulin sensitivity and/or beta-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. beta-Cell function (disposition index [DI]) was calculated as S(i) x AIRg, where S(i) 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 cm(2); P = 0.03) and SCF (196.5 +/- 18.0 vs. 227.7 +/- 19.9 cm(2); P < 0.001) areas, greater S(i) (4.7 +/- 0.5 vs. 3.3 +/- 0.3 x 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. S(i) 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 beta-cell function, suggesting that this degree of lifestyle modifications may be limited in preventing type 2 diabetes over the long term. [ABSTRACT FROM AUTHOR]

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 beta-cell function with age is related to increases in intra-abdominal fat or age per se, we studied 220 healthy subjects with fasting glucose <6.1 mmol/l (89 men and 131 women, aged 26-75 years, BMI 18.7-40.4 kg/m(2)). The insulin sensitivity index (S(i)) and the acute insulin response to glucose (AIRg) were determined, and from these beta-cell function was estimated as the disposition index (S(i) x AIRg). Intra-abdominal fat and subcutaneous fat areas were quantified by computed tomography. S(i) (5.40 +/- 0.5 vs. 7.86 +/- 0.7 x10(-5) min(-1)/[pmol/l]), P < 0.01) was decreased and intra-abdominal fat (117 +/- 10 vs. 81 +/- 9 cm(2), P < 0.05) was increased in the oldest (age 60-75 years) versus the youngest (age 26-44 years) quartile. The hyperbolic relationship between S(i) and AIRg was present independent of age; thus, beta-cell function measured as the disposition index (1,412 +/- 120 vs. 2,125 +/- 150 x10(-5) min(-1), P < 0.01) was lower in the oldest versus the youngest quartile. In multiple regression, intra-abdominal fat (r = -0.470, P < 0.001) but not age was associated with S(i), 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 beta-cell function, age has an independent effect on beta-cell function that may contribute to the increased prevalence of type 2 diabetes in older populations. [ABSTRACT FROM AUTHOR]

Gestational diabetes mellitus (GDM) is associated with an increased risk of developing type 2 diabetes (T2D). A third to half of women with a history of GDM develop T2D within 3-5 years and 70% develop T2D after 10 years. We hypothesized that women who did not meet the Carpenter/Coustan criteria for GDM because they had only one abnormal value on the 100-g 3-hour oral glucose tolerance test (OGTT) were at increased risk of developing T2D. To address this hypothesis, we performed a cohort study of women who delivered between 1985 and 2002 at Group Health in Washington state. Eligible women (N=6,237; age 32.1±5.7 years, mean±SD) were enrolled ≥1 year before delivery and received subsequent care at Group Health. T2D was ascertained through 2005 based on ICD-9 codes, pharmacy data for insulin or oral agents, or fasting glucose ≥126 and/or nonfasting glucose ≥200 mg/dl on two occasions. During pregnancy, 3,671 women had a normal OGTT; 1,252 had one abnormal value; and 1,313 had GDM (≥2 abnormal values based on the Carpenter/Coustan criteria: fasting glucose ≥95, 1-hour ≥180, 2-hour ≥155, 3-hour ≥140 mg/dl). Subsequent T2D was diagnosed in 49 women (1.3%) with a normal OGTT, 31 (2.5%) with one abnormal value, and 67 (5.1%) with GDM. The median follow-up duration was 7 (interquartile range 3.5-11.8) years. Women with one abnormal result were at increased risk of developing T2D compared to those with normal values (hazard ratio, HR, 2.20, 95%CI 1.41-3.45; P=0.001) adjusting for age and multiparity. Of the women with one abnormal value, 227 (18.1%) had an abnormal fasting, 362 (29.0%) had an abnormal 1-hour, 460 (36.7%) had an abnormal 2-hour, and 203 (16.2%) had an abnormal 3-hour glucose. T2D developed in 6.1% of those with an isolated abnormal fasting, 1.9% with an abnormal l-hour, 1.7% with an abnormal 2-hour, and 1% with an abnormal 3-hour glucose. T2D among these women with one abnormal value was significantly associated with an abnormal fasting (HR 5.83, 95%CI 3.25-10.46; P<0.001), but not with an abnormal 1-hour (HR 1.70, 95%CI 0.76-3.76; P=0.2), 2-hour (HR 1.80, 95%CI 0.91-3.57; P=0.09) or 3-hour glucose (HR 0.38, 95%CI 0.05-2.76; P=0.3) adjusting for age and multiparity. While having one abnormal OGTT value does not meet criteria for GDM, the risk of developing T2D is elevated in these women. Therefore, women with a single abnormal OGTT value during pregnancy, particularly a fasting value, should be considered for surveillance for the future development of T2D. [ABSTRACT FROM AUTHOR]

Women with a history of gestational diabetes have an increased risk of developing type 2 diabetes (T2D). We evaluated whether glucose values from the gestational diabetes screening test (50-g, l-hour oral glucose challenge test, OGCT) were also associated with the future risk of T2D in a cohort study of women who delivered between 1985 and 2002 at Group Health in Washington state. The women (N=26,248) had an OGCT during pregnancy, were enrolled at least 1 year before delivery and received subsequent care at Group Health. They did not have known diabetes prior to pregnancy or subsequent type 1 diabetes. T2D was ascertained through 2005 based on inpatient and outpatient ICD-9 codes, pharmacy data for insulin or oral medications, or fasting glucose ≥126 mg/dl and/or nonfasting glucose ≥200 mg/dl on two separate occasions. Women were 30.0±6.2 (mean±SD) years old at the index pregnancy, 39.5% were multiparous, 18.3% had an OGCT result ≥140 mg/dl, and 5.1% received a diagnosis of gestational diabetes based on ICD-9 codes and/or the 100-g, 3-hour oral glucose tolerance test. Subsequent T2D was diagnosed in 289 women (1.1%) with a median follow-up duration of 6.4 (interquartile range 3.3-11) years. The mean OGCT result was higher in women with subsequent T2D compared to those without (136.1±31.9 versus 115.6±26.5.mg/dl; P<0.001). This association remained significant after adjusting for age, multiparity, and gestational diabetes (P<0.001). The risk of developing T2D increased across OGCT quartiles: hazard ratio, HR, 1.95 (95%CI 1.19-3.19; P=0.008) for 97.1 - 113 mg/dl, HR 2.25 (95%CI 1.40-3.60; P=0.001) for 113.1 -134 mg/dl, and HR 3.87 (95%CI 2.46-6.12; P<0.001) for ≥134.1 mg/dl compared to the reference quartile (OGCT≤97 mg/dl) adjusting for age, multiparity, and gestational diabetes. Among women with OGCT results below the threshold for further testing for gestational diabetes, those with an OGCT result between 97.1 and 134 mg/dl had a 2 fold increased risk of developing T2D relative to women with the lowest OGCT values. Thus, OGCT results may help identify those at risk of developing T2D independent of gestational diabetes. [ABSTRACT FROM AUTHOR]

Recent suggestions for hospital care of diabetic patients include the maintenance of serum glucose leves ≤ 120 mg/dl. Since insulin is the most frequently erred medication in hopitals, and since the intravenous administration of insulin is a complex nursing service, we devised a computer-based protocol for hospital nurses to determine the appropriate dose of intravenous insulin for an individual patient, and made it available to every nursing unit in the 3 general hospitals in Columbus, Georgia via a secure web-based interface. The calculation to determine insulin dose involved the development of a new algorithm, based on available formulae. In addition, a separate sequential algorithm was developed to reduce the risk of hypoglycemia. These joint algorithms were tested on 171 hospitalized diabetic patients, from whom 7544 blood sugar measurements were determined. Mean glucose levels for the initial three serum glucose levels were 169 +/- 10.5 mg/dl. Mean levels for the last six determinations, just prior to the cessation of intravenous insulin were 118 +/- 3.41 mg/dl (p<0.0001). The distribution of the last six glucose levels conformed to a parametric curve, with a median of 105 mg/dl. Less than 0.6% of all values were < 60 mg/dl. The algorithm was then placed on a secure server and linked to the hospital computer systems of the three area general hospitals. It is available to any hospital nurse via a secure web-based interface. This system is the first city-wide program to standardize intravenous insulin administration. We conclude that a web-based set of computer algorithms may provide a reliable, effective, and safe method for the use of intravenous insulin therapy for the hospital units of an entire city. [ABSTRACT FROM AUTHOR]

The article looks at the findings of a U.S. study about the association of polymorphisms in genes encoding the transcription factor 7-like 2 (TCF7L2) and the pancreatic β-cell adenosine triphosphate (ATP)-sensitive potassium channel subunit Kirb6.2 (KCNJ11) with diabetes mellitus (DM) in Japanese Americans. The study found that only 2.4% of the subjects had the at risk T allele at rs12255372 which was not associated with DM. There was no association found between DM and the KCNJ11 variant.

The relative importance of impaired fasting glucose (IFG) and impaired glucose tolerance (IGT) as "prediabetes" conditions is debated. We examined whether subjects with isolated IFG, isolated IGT or combined IFG/IGT carry different risks for the development of diabetes. Prospective analysis was performed in 509 non-diabetic Japanese Americans (262M/247F, mean age 52.1±12.0 y, BM124.1±3.2 kg/m²) with normal glucose tolerance (NGT) (n=253), isolated IFG (n=61), isolated IGT (n=117) and IFG/IGT (n=78) by an oral glucose tolerance test at baseline. Two (0.8%) NGT, 3 (4.9%) isolated IFG, 18 (15.4%) isolated IGT, and 24 (30.8%) IFG/IGT subjects developed diabetes at 5-y follow-up (n=455), while 8 (3.2%), 5 (8.2%), 22 (18.8%) and 31 (39.7%) developed diabetes at 10-y follow-up (n=399), respectively. At baseline, gender was a major determinant of abnormal glucose tolerance with men more likely to have isolated IFG (OR=2.1 [95% CI 1.04-4.1]) and IFG/IGT (OR=2.2 [1.1-4.3]), while women were more likely to have isolated IGT compared to NGT (OR=2.4 [1.4-4.0]) after adjusting for age, BMI, intra-abdominal fat, fasting insulin, and early insulin release (ΔI[sub 0-30]/ΔG[sub 0-30]). Baseline isolated IGT and IFG/IGT predicted the development of diabetes at both 5- (OR=18.9 [3.9-90.4] and OR=41.9 [8.4-208.7] respectively) and 10-y follow-up (OR=7.0 [2.8-17.6] and OR=23.1 [8.3-64.0] respectively) compared to NGT after adjusting for age, gender, BMI, intra-abdominal fat, fasting insulin, and early insulin release. In contrast, isolated IFG did not predict the future development of diabetes (OR=5.3 [0.8-35.3] at 5y and OR=2.2 [0.6-7.5] at 10y respectively). Thus, having isolated IGT at baseline was associated with a higher risk of development of diabetes at 5-y follow-up compared to isolated IFG (OR=5.0 [1.3-19.2]). In conclusion, IGT is a more important risk factor than isolated IFG for the development of diabetes in Japanese Americans, with women being at particular risk for IGT. The 2-hour rather than the fasting glucose provides greater information for the prediction of future diabetes in this population. ADA-Funded Research [ABSTRACT FROM AUTHOR]