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Context: Type 2 diabetes mellitus (DM) is associated with higher bone mineral density (BMD) and paradoxically with increased fracture risk. It is not known if low BMD, central to fracture prediction in older adults, identifies fracture risk in patients with DM., Objective: To determine if femoral neck BMD T score and the World Health Organization Fracture Risk Algorithm (FRAX) score are associated with hip and nonspine fracture risk in older adults with type 2 DM., Design, Setting, and Participants: Data from 3 prospective observational studies with adjudicated fracture outcomes (Study of Osteoporotic Fractures [December 1998-July 2008]; Osteoporotic Fractures in Men Study [March 2000-March 2009]; and Health, Aging, and Body Composition study [April 1997-June 2007]) were analyzed in older community-dwelling adults (9449 women and 7436 men) in the United States., Main Outcome Measure: Self-reported incident fractures, which were verified by radiology reports., Results: Of 770 women with DM, 84 experienced a hip fracture and 262 a nonspine fracture during a mean (SD) follow-up of 12.6 (5.3) years. Of 1199 men with DM, 32 experienced a hip fracture and 133 a nonspine fracture during a mean (SD) follow-up of 7.5 (2.0) years. Age-adjusted hazard ratios (HRs) for 1-unit decrease in femoral neck BMD T score in women with DM were 1.88 (95% confidence interval [CI], 1.43-2.48) for hip fracture and 1.52 (95% CI, 1.31-1.75) for nonspine fracture, and in men with DM were 5.71 (95% CI, 3.42-9.53) for hip fracture and 2.17 (95% CI, 1.75-2.69) for nonspine fracture. The FRAX score was also associated with fracture risk in participants with DM (HRs for 1-unit increase in FRAX hip fracture score, 1.05; 95% CI, 1.03-1.07, for women with DM and 1.16; 95% CI, 1.07-1.27, for men with DM; HRs for 1-unit increase in FRAX osteoporotic fracture score, 1.04; 95% CI, 1.02-1.05, for women with DM and 1.09; 95% CI, 1.04-1.14, for men with DM). However, for a given T score and age or for a given FRAX score, participants with DM had a higher fracture risk than those without DM. For a similar fracture risk, participants with DM had a higher T score than participants without DM. For hip fracture, the estimated mean difference in T score for women was 0.59 (95% CI, 0.31-0.87) and for men was 0.38 (95% CI, 0.09-0.66)., Conclusions: Among older adults with type 2 DM, femoral neck BMD T score and FRAX score were associated with hip and nonspine fracture risk; however, in these patients compared with participants without DM, the fracture risk was higher for a given T score and age or for a given FRAX score.

Context: Type 2 diabetes is associated with higher fracture risk at a given bone mineral density. Advanced glycation endproducts (AGEs) accumulate in bone collagen with age and diabetes and may weaken bone., Objective: The aim was to determine whether urine pentosidine, an AGE, was associated with fractures in older adults with and without diabetes., Design: We performed an observational cohort study., Setting: We used data from the Health, Aging and Body Composition prospective study of white and black, well-functioning men and women ages 70-79 yr., Participants: Participants with (n = 501) and without (n = 427) diabetes were matched on gender, race, and study site., Predictor: Urine pentosidine was assayed from frozen stored baseline specimens., Main Outcome Measures: Incident clinical fractures and baseline vertebral fractures were measured., Results: Despite higher bone mineral density, clinical fracture incidence (14.8 vs. 12.6%) and vertebral fracture prevalence (2.3 vs. 2.9%) were not lower in those with diabetes (P > 0.05). In multivariable models, pentosidine was associated with increased clinical fracture incidence in those with diabetes [relative hazard, 1.42; 95% confidence interval (CI), 1.10, 1.83, for 1 sd increase in log pentosidine] but not in those without diabetes (relative hazard, 1.08; 95% CI, 0.79, 1.49; P value for interaction = 0.030). In those with diabetes, pentosidine was associated with increased vertebral fracture prevalence (adjusted odds ratio, 5.93; 95% CI, 2.08, 16.94, for 1 sd increase in log pentosidine) but not in those without diabetes (adjusted odds ratio, 0.74; 95% CI, 0.30, 1.83; P value for interaction = 0.005)., Conclusions: Higher pentosidine levels are a risk factor for fracture in older adults with diabetes and may account in part for reduced bone strength in type 2 diabetes.

Objective: The purpose of this study was to examine age of diabetes diagnosis in youth who have a parent with diabetes by diabetes type and whether the parent's diabetes was diagnosed before or after the youth's birth., Research Design and Methods: The cohort comprised SEARCH for Diabetes in Youth Study participants (diabetes diagnosis 2001-2005) with a diabetic parent. SEARCH is a multicenter survey of youth with diabetes diagnosed before age 20 years., Results: Youth with type 2 diabetes were more likely to have a parent with either type 1 or type 2 diabetes (mother 39.3%; father 21.2%) than youth with type 1 diabetes (5.3 and 6.7%, respectively, P < 0.001 for each). Type 2 diabetes was diagnosed 1.68 years earlier among those exposed to diabetes in utero (n = 174) than among those whose mothers' diabetes was diagnosed later (P = 0.018, controlled for maternal diagnosis age, paternal diabetes, sex, and race/ethnicity). Age at diagnosis of type 1 diabetes for 269 youth with and without in utero exposure did not differ significantly (difference 0.96 year, P = 0.403 after adjustment). Controlled for the father's age of diagnosis, father's diabetes before the child's birth was not associated with age at diagnosis (P = 0.078 for type 1 diabetes; P = 0.140 for type 2 diabetes)., Conclusions: Type 2 diabetes was diagnosed at younger ages among those exposed to hyperglycemia in utero. Among youth with type 1 diabetes, the effect of the intrauterine exposure was not significant when controlled for mother's age of diagnosis. This study helps explain why other studies have found higher age-specific rates of type 2 diabetes among offspring of women with diabetes.

Purpose: The study compares the risk of incident diabetes associated with fasting plasma glucose levels in the normal range, controlling for other risk factors., Methods: We identified 46,578 members of Kaiser Permanente Northwest who had fasting plasma glucose levels less than 100 mg/dL between January 1, 1997, and December 31, 2000, and who did not previously have diabetes or impaired fasting glucose. After assigning subjects to 1 of 4 categories (<85, 85-89, 90-94, or 95-99 mg/dL), we followed them until they developed diabetes, died, or left the health plan, or until April 30, 2007. We used Cox regression analysis to estimate the risk of incident diabetes, adjusted for age, sex, body mass index, blood pressure, lipids, smoking, cardiovascular disease, and hypertension., Results: Subjects developed diabetes at a rate of less than 1% per year during a mean follow-up of 81.0 months. Each milligram per deciliter of fasting plasma glucose increased diabetes risk by 6% (hazard ratio [HR] 1.06, 95% confidence interval [CI], 1.05-1.07, P < .0001) after controlling for other risk factors. Compared with those with fasting plasma glucose levels less than 85 mg/dL, subjects with glucose levels of 95 to 99 mg/dL were 2.33 times more likely to develop diabetes (HR 2.33; 95% CI, 1.95-2.79; P < .0001). Subjects in the 90 to 94 mg/dL group were 49% more likely to progress to diabetes (HR 1.49; 95% CI, 1.23-1.79; P <.0001). All other risk factors except sex were significantly associated with a diabetes diagnosis., Conclusions: The strong independent association between the level of normal fasting plasma glucose and the incidence of diabetes after controlling for other risk factors suggests that diabetes risk increases as fasting plasma glucose levels increase, even within the currently accepted normal range.

Objective: We sought to estimate the rate of progression from newly acquired (incident) impaired fasting glucose (IFG) to diabetes under the old and new IFG criteria and to identify predictors of progression to diabetes., Research Design and Methods: We identified 5,452 members of an HMO with no prior history of diabetes, with at least two elevated fasting glucose tests (100-125 mg/dl) measured between 1 January 1994 and 31 December 2003, and with a normal fasting glucose test before the two elevated tests. All data were obtained from electronic records of routine clinical care. Subjects were followed until they developed diabetes, died, left the health plan, or until 31 December 2005., Results: Overall, 8.1% of subjects whose initial abnormal fasting glucose was 100-109 mg/dl (added IFG subjects) and 24.3% of subjects whose initial abnormal fasting glucose was 110-125 mg/dl (original IFG subjects) developed diabetes (P < 0.0001). Added IFG subjects who progressed to diabetes did so within a mean of 41.4 months, a rate of 1.34% per year. Original IFG subjects converted at a rate of 5.56% per year after an average of 29.0 months. A steeper rate of increasing fasting glucose; higher BMI, blood pressure, and triglycerides; and lower HDL cholesterol predicted diabetes development., Conclusions: To our knowledge, these are the first estimates of diabetes incidence from a clinical care setting when the date of IFG onset is approximately known under the new criterion for IFG. The older criterion was more predictive of diabetes development. Many newly identified IFG patients progress to diabetes in <3 years, which is the currently recommended screening interval.

The authors examined whether obesity alone or as part of the metabolic syndrome (MS) increases coronary heart disease (CHD) risk in type 2 diabetes mellitus (T2DM) among 2970 adults aged 30-79 years in a French national sample. MS was defined as T2DM plus self-report of 2 or more of the following: body mass index >30 kg/m(2), diagnosed hypertension, or diagnosed dyslipidemia. A subsample with physician-reported data (n =841) was further classified with measured hypertension and dyslipidemia. Weight distribution included normal (21%), overweight (42%), and obese (37%). A 20% increased odds of CHD was estimated for every 5-kg/m(2) body mass index increase (P=.0001). MS was associated with a more than 2-fold higher risk of CHD compared with T2DM without MS (P<.0001, multivariate-adjusted [both samples]). With MS stratified by high-density lipoprotein cholesterol (<1.5 vs > or =1.5 mmol/L), compared with no MS, the odds ratio for CHD was 2.8 (normal-level high-density lipoprotein MS; 95% confidence interval, 1.8-4.5) and 1.5 (high-level high-density lipoprotein MS; 95% confidence interval, 0.8-2.9). The authors suggest that obesity alone--and particularly when the MS is present--increases CHD risk in patients with T2DM. High levels of high-density lipoprotein may modify this relationship.

Objective: To determine whether adults diagnosed with type 2 diabetes from age 18 to 44 years more aggressively develop clinical complications after diagnosis than adults diagnosed at >or=45 years of age., Research Design and Methods: We compared outcomes among 7844 adults in a health maintenance organization who were newly diagnosed with type 2 diabetes between 1996 and 1998. We abstracted clinical data from electronic medical, laboratory, and pharmacy records. To adjust for length of follow-up and sex, we used proportional hazards models to compare incident complication rates through 2001 between onset groups (mean follow-up 3.9 years). To adjust for the increasing prevalence of macrovascular disease with advancing age, onset groups were matched by age and sex to control subjects without diabetes for macrovascular outcomes., Results: Adults with early-onset type 2 diabetes were 80% more likely to begin insulin therapy than those with usual-onset type 2 diabetes (hazards ratio [HR] 1.8, 95% CI 1.5-2.0), despite a similar average time to requiring insulin ( approximately 2.2 years). Although the combined risk of microvascular complications did not differ overall, microalbuminuria was more likely in early-onset type 2 diabetes than usual-onset type 2 diabetes (HR 1.2, 95% CI 1.1-1.4). The hazard of any macrovascular complication in early-onset type 2 diabetic patients compared with control subjects was twice as high in usual-onset type 2 diabetic patients compared with control subjects (HR 7.9 vs. 3.8, respectively). Myocardial infarction (MI) was the most common macrovascular complication, and the hazard of developing an MI in early-onset type 2 diabetic patients was 14-fold higher than in control subjects (HR 14.0, 95% CI 6.2-31.4). In contrast, adults with usual-onset type 2 diabetes had less than four times the risk of developing an MI compared with control subjects (HR 3.7, P < 0.001)., Conclusions: Early-onset type 2 diabetes appears to be a more aggressive disease from a cardiovascular standpoint. Although the absolute rate of cardiovascular disease (CVD) is higher in older adults, young adults with early-onset type 2 diabetes have a much higher risk of CVD relative to age-matched control subjects.

Objective: To estimate the prevalence and incidence of congestive heart failure (CHF) in populations with and without type 2 diabetes and to identify risk factors for diabetes-associated CHF., Research Design and Methods: We searched the inpatient and outpatient electronic medical records of 9,591 individuals diagnosed with type 2 diabetes before 1 January 1997 and those of an age- and sex-matched control group without diabetes for a diagnosis of CHF. Among those without a baseline diagnosis of CHF, we searched forward for 30 months for incident cases of CHF. We constructed multiple logistic regression models to identify risk factors for both prevalent and incident CHF., Results: CHF was prevalent in 11.8% (n = 1,131) of diabetic subjects and 4.5% (n = 435) of control subjects at baseline. We observed incident cases of CHF in 7.7% of diabetic subjects free of CHF at baseline (650 of 8,460) and in 3.4% of control subjects (314 of 9,156). In diabetic subjects, age, diabetes duration, insulin use, ischemic heart disease, and elevated serum creatinine were independent risk factors for both prevalent and incident CHF. Better glycemic control at baseline, and improved glycemic and blood pressure control at follow-up predicted the development of CHF., Conclusions: Despite controlling for age, duration of diabetes, presence of ischemic heart disease, and presence of hypertension, insulin use was associated with both prevalent and incident CHF. Why insulin use and better glycemic control both at baseline and follow-up independently predicted CHF deserves further study.

Objective: To determine whether adults diagnosed with type 2 diabetes at 18-44 years of age (early type 2 diabetes) have different metabolic profiles at diagnosis than adults diagnosed at > or =45 years of age (usual type 2 diabetes)., Research Design and Methods: Within a health maintenance organization, we studied characteristics among 2,437 adults newly diagnosed with type 2 diabetes between 1996 and 1998 who had measured weight, HbA(1c), blood pressure, and cholesterol within 3 months of diagnosis. We abstracted clinical data from electronic medical records. We compared mean and proportional differences with parametric t tests and chi(2) analyses, respectively. We used multiple logistic regression to identify the factors independently associated with the onset group (early vs. usual type 2 diabetes)., Results: There was an inverse linear relationship between BMI and age at diagnosis of type 2 diabetes (P < 0.001). On univariate analysis, adults with early type 2 diabetes were more obese (BMI 39 vs. 33 kg/m(2), P < 0.001), were more likely to be female (P = 0.04), had slightly worse glycemic control (HbA(1c) 7.7 vs. 7.5%, P = 0.03), had a higher prevalence of diastolic hypertension (37 vs. 26%, P < 0.001), despite a lower prevalence of systolic hypertension (34 vs. 55%, P < 0.001), and had an equally high rate of abnormal lipids (82 vs. 78%, P = 0.13) than adults with usual type 2 diabetes. BMI, female gender, cholesterol, and diastolic and systolic blood pressure remained independently associated with onset group at multivariate analysis., Conclusions: Although both onset groups were on average obese, the inverse linear relationship of obesity and age of diabetes onset that we observed suggests that obesity is a continuous risk rather than a threshold risk for diabetes onset. Both onset groups had a high prevalence of cardiovascular disease risk factors.

Objective: To determine the characteristics that influence glycemic control among insulin-using adults with type 2 diabetes., Research Design and Methods: We studied all 1,333 eligible members of a large not-for-profit health maintenance organization who responded to a 1997 survey. We tested associations among demographic, treatment, and psychometric variables with mean 1997 HbA1c values. The Problem Areas in Diabetes (PAID) instrument was used to assess the emotional effect of living with diabetes, and the Short Form 12 Physical Function Scale was used to assess the effect of physical limitations on daily activities. Based on differences between and within treatment groups, we built models to predict glycemic control for subgroups of subjects who were using insulin alone and those who were using insulin in combination with an oral hypoglycemic agent., Results: Younger age, lower BMI, and increased emotional distress about diabetes (according to the PAID scale) were all significant predictors (P < 0.05) of worse glycemic control. However, except among individuals with an HbA1c level of >8.0 who were receiving combination therapy, only approximately 10% of the variance in glycemic control could be predicted by demographic, treatment, or psychometric characteristics., Conclusions: Personal characteristics explain little of the variation in glycemic control in insulin-using adults with type 2 diabetes. Possible explanations are that the reduced complexity of control in type 2 diabetes makes the disease less sensitive to personal factors than control in type 1 diabetes, that health-related behavior is less driven by personal and environmental characteristics among older individuals, or that, in populations exposed to aggressive glycemic control with oral hypoglycemic agents and nurse care managers, personal differences become largely irrelevant.