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Objective: Although management of type 1 diabetes improved dramatically in the 1980s, the effect on mortality is not clear.Research Design and Methods: We report trends in 30-year mortality using the Allegheny County (Pennsylvania) childhood-onset (age <18 years) type 1 diabetes registry (n = 1,075) with diagnosis from 1965-1979, by dividing the cohort into three diagnosis year cohorts (1965-1969, 1970-1974, and 1975-1979). Local (Allegheny County) mortality data were used to calculate standardized mortality ratios (SMRs).Results: As of 1 January 2008, vital status was ascertained for 97.0% of participants (n = 1,043) when mean age ± SD and duration of diabetes were 42.8 ± 8.0 and 32.0 ± 7.6 years, respectively. The 279 deaths (26.0%) observed were 7 times higher than expected (SMR 6.9 [95% CI 6.1-7.7]). An improving trend in SMR was seen by diagnosis cohort at 30 years of diabetes duration (9.3 [7.2-11.3], 7.5 [5.8-9.2], and 5.6 [4.0-7.2] for 1965-1969, 1970-1974, and 1975-1979, respectively). Although no sex difference in survival was observed (P = 0.27), female diabetic patients were 13 times more likely to die than age-matched women in the general population (SMR 13.2 [10.7-15.7]), much higher than the SMR for men (5.0 [4.0-6.0]). Conversely, whereas 30-year survival was significantly lower in African Americans than in Caucasians (57.2 vs. 82.7%, respectively; P < 0.001), no differences in SMR were seen by race.Conclusions: Although survival has clearly improved, those with diabetes diagnosed most recently (1975-1979) still had a mortality rate 5.6 times higher than that seen in the general population, revealing a continuing need for improvements in treatment and care, particularly for women and African Americans with type 1 diabetes. [ABSTRACT FROM AUTHOR]

Objective: To evaluate the association of successive percutaneous coronary intervention (PCI) modalities with balloon angioplasty (BA), bare-metal stent (BMS), drug-eluting stents (DES), and pharmacotherapy over the last 3 decades with outcomes among patients with diabetes in routine clinical practice.Research Design and Methods: We examined outcomes in 1,846 patients with diabetes undergoing de novo PCI in the multicenter, National Heart, Lung, and Blood Institute-sponsored 1985-1986 Percutaneous Transluminal Coronary Angioplasty (PTCA) Registry and 1997-2006 Dynamic Registry. Multivariable Cox regression models were used to estimate the adjusted risk of events (death/myocardial infarction [MI], repeat revascularization) over 1 year.Results: Cumulative event rates for postdischarge (31-365 days) death/MI were 8% by BA, 7% by BMS, and 7% by DES use (P = 0.76) and for repeat revascularization were 19, 13, and 9% (P < 0.001), respectively. Multivariable analysis showed a significantly lower risk of repeat revascularization with DES use when compared with the use of BA (hazard ratio [HR] 0.41 [95% CI 0.29-0.58]) and BMS (HR 0.55 [95% CI 0.39-0.76]). After further adjustment for discharge medications, the lower risk for death/MI was not statistically significant for DES when compared with BA.Conclusions: In patients with diabetes undergoing PCI, the use of DES is associated with a reduced need for repeat revascularization when compared with BA or BMS use. The associated death/MI benefit observed with the DES versus the BA group may well be due to greater use of pharmacotherapy. [ABSTRACT FROM AUTHOR]

Objective: To quantify total diabetes care received (generalist or specialist) from diagnosis onward and its association with the incidence of diabetes complications in a representative cohort of patients with type 1 diabetes.Research Design and Methods: A total of 429 subjects from the Pittsburgh Epidemiology of Diabetes Complications Study, a prospective follow-up study of childhood-onset type 1 diabetic subjects first seen between 1986 and 1988 (mean age 28 years, mean duration 19 years), followed biennially for up to 10 years were studied. Specialist care was defined as care received from a board-certified endocrinologist, diabetologist, or diabetes clinic and quantified as the percent of diabetes duration spent in specialist care.Results: There was a significant trend for a higher incidence of neuropathy, overt nephropathy, and coronary artery disease with lower use of specialist care. Multivariate analyses controlling for diabetes duration, demographic characteristics, health care practices, and physiological risk factors demonstrated that higher past use of specialist care was found to be significantly protective against the development of overt nephropathy (risk ratio 0.43, 95% CI 0.21-0.88) and neuropathy (0.54, 0.35-0.83) and weakly protective against coronary artery disease (0.65, 0.37-1.1).Conclusions: A higher proportion of diabetes duration spent in specialist care may result in delayed development of certain diabetes complications independent of other risk factors. This study thus supports the concept that the benefits of specialist care should be available to all patients with type 1 diabetes. [ABSTRACT FROM AUTHOR]

Objective: To determine whether diabetes care characteristics and glycemic control differ by use of specialist care in a representative cohort of patients with type 1 diabetes.Research Design and Methods: Health care, sociodemographic characteristics, and glycemic control were compared between participants in the Pittsburgh Epidemiology of Diabetes Complications Study who reported receiving specialist care (n = 212) and those who did not (n = 217). Specialist care was defined as having received care from an endocrinologist or diabetologist or diabetes clinic attendance during the last year.Results: Patients who reported receiving specialist care were more likely to be female, to have an education level beyond high school, to have an annual household income >$20,000, and to have health insurance. Additionally, patients receiving specialist care were more likely to have received diabetes education during the previous 3 years, to have knowledge of HbAlc testing and to have received that test during the previous 6 months, to have knowledge of the Diabetes Control and Complications Trial results, to self-monitor blood glucose, and to inject insulin more than twice daily. A lower HbA1 level was associated with specialist care versus generalist care (9.7 vs. 10.3%; P = 0.0006) as were higher education and income levels. Multivariate analyses suggest that the lower HbA1 levels observed in patients receiving specialist care were restricted to patients with an annual income >$20,000.Conclusions: Specialist care was associated with higher levels of participation in diabetes self-care practices and a lower HbA1 level. Future efforts should research and address the failure of patients with low incomes to benefit from specialist care. [ABSTRACT FROM AUTHOR]

Objective: Little is known concerning the primary cause(s) of mortality in type 1 diabetes responsible for the excess mortality seen in this population., Research Design and Methods: The Allegheny County (Pennsylvania) childhood-onset (age < 18 years) type 1 diabetes registry (n = 1,075) with diagnosis from 1965 to 1979 was used to explore patterns in cause-specific mortality. Cause of death was determined by a mortality classification committee of at least three physician epidemiologists, based on the death certificate and additional records surrounding the death., Results: Vital status for 1,043 (97%) participants was ascertained as of 1 January 2008, revealing 279 (26.0%) deaths overall (141 females and 138 males). Within the first 10 years after diagnosis, the leading cause of death was acute diabetes complications (73.6%), while during the next 10 years, deaths were nearly evenly attributed to acute (15%), cardiovascular (22%), renal (20%), or infectious (18%) causes. After 20 years' duration, chronic diabetes complications (cardiovascular, renal, or infectious) accounted for >70% of all deaths, with cardiovascular disease as the leading cause of death (40%). Women (P < 0.05) and African Americans (P < 0.001) have significantly higher diabetes-related mortality rates than men and Caucasians, respectively. Standardized mortality ratios (SMRs) for non-diabetes-related causes do not significantly differ from the general population (violent deaths: SMR 1.2, 95% CI 0.6-1.8; cancer: SMR 1.2, 0.5-2.0)., Conclusions: The excess mortality seen in type 1 diabetes is almost entirely related to diabetes and its comorbidities but varies by duration of diabetes and particularly affects women and African Americans.

Objective: African American youth have lower insulin sensitivity than their Caucasian peers, but the metabolic pathways responsible for this difference remain unknown. Free fatty acids (FFAs) are associated with insulin resistance through the Randle cycle. The present investigation determined whether elevating FFA is more deleterious to insulin sensitivity in African American than in Caucasian adolescents., Research Design and Methods: Insulin sensitivity (3-h hyperinsulinemic-euglycemic clamp) was evaluated in 22 African American and 21 Caucasian adolescents on two occasions: 1) infusion of normal saline and 2) infusion of 20% intralipid., Results: During intralipid infusion, fasting insulin and C-peptide concentrations increased while fasting glucose and basal glucose turnover did not change in either group. Insulin sensitivity decreased similarly in African American (normal saline 7.65 +/- 0.61 vs. intralipid 5.15 +/- 0.52 micromol x kg(-1) x min(-1) per pmol/l) and Caucasian subjects (normal saline 8.97 +/- 0.85 vs. intralipid 5.96 +/- 0.56 micromol x kg(-1) x min(-1) per pmol/l) (P < 0.001)., Conclusions: African American and Caucasian adolescents respond to FFA elevation similarly through increased fasting insulin secretion to maintain fasting glucose homeostasis and reduced peripheral glucose uptake and insulin resistance. Thus, African American adolescents are not more susceptible to FFA-induced insulin resistance than Caucasian youth.

Objective: To examine the relationships between microalbuminuria and the development of overt diabetic nephrology, elevated blood pressure, and a more atherogenic lipid profile; and to identify risk factors for the development of microalbuminuria in individuals with IDDM. Microalbuminuria has been associated with the subsequent development of overt diabetic nephropathy in individuals with IDDM. It is associated with elevated blood pressure and a more atherogenic lipid profile, but the temporal relationship between the development of microalbuminuria and the changes in these factors is unclear., Research Design and Methods: Baseline characteristics were examined in 256 individuals with IDDM who had normal albumin excretion (urinary AER < or = 20 micrograms/min in > or = 2 timed urine collections) and were re-examined 2 yr later., Results: At follow-up, 24 had developed microalbuminuria (AER 20-200 micrograms/min in > or = 2 timed urine collections) and 1 had developed overt nephropathy (AER > 200 micrograms/min). Overall, the significant independent predictors of microalbuminuria were HbA1 (P < 0.001), low-density lipoprotein (P < 0.01), duration of IDDM (P < 0.05), and systolic blood pressure (P = 0.05). Sex-specific analyses showed HbA1, age, and baseline AER were particularly important for men; whereas, for women, the main predictors were duration of IDDM and triglycerides. Duration-specific analyses showed that HbA1 was an important predictor both for individuals with < and > 20-yr duration. Low-density lipoprotein cholesterol was more important for subjects with shorter durations; whereas triglycerides were important for those with longer durations., Conclusions: These results suggest that glycemic control, age or duration of IDDM, disturbed lipids, and possibly elevated blood pressure all may contribute to the development of microalbuminuria; and, further, that the adverse cardiovascular risk profile seen in individuals with overt nephropathy may begin to develop even before the detection of microalbuminuria.

Objective: To determine the descriptive epidemiological patterns of the secondary attack rate of insulin-dependent diabetes mellitus (IDDM) among siblings of probands through older ages., Research Design and Methods: A family history analysis was performed on 1774 IDDM probands who were diagnosed or seen within 1 yr of diagnosis at Children's Hospital of Pittsburgh from 1 January 1950 through 31 December 1981. The probands were discharged on insulin and were diagnosed at less than 17 yr of age. The time frame permitted the risk of IDDM for siblings of probands to be calculated over a broad spectrum of age., Results: Risk estimates for the 3966 full natural siblings through 10, 20, and 30 yr of age were 1.6, 4.1, and 6.3%, respectively. Secondary attack rates were equivalent for male and female siblings through 15 yr of age (3%); however, the risk to males increased an additional 4% between 16 and 30 yr of age compared with 2.5% for females (P = 0.01). There was no evidence of an excess sex concordance among affected sibling pairs., Conclusions: Males have a greater secondary attack rate of IDDM at older ages than females. This may be due to an increased exposure to environmental agents among males or protective influences operating among females.

The need for a standardized and valid means of assessing diabetic neuropathy has been increasingly recognized. To identify potential components of such an assessment, interobserver variation (neurologist and internist) of a standard neurologic examination and the comparability of this examination with vibratory and thermal sensitivity testing was studied. The study population comprised the first 100 participants in a neuropathy substudy of 25- to 34-yr-old subjects with insulin-dependent diabetes mellitus taking part in a cohort follow-up study. Symptoms of dysesthesias, paresthesias, and burning, aching, or stabbing pain revealed good interobserver agreement. Signs of neuropathy, more prevalent in the great toe than index finger, showed poor interobserver agreement for vibration, but fair interobserver agreement for touch and pinprick. Mean quantitative sensory thresholds differed significantly by clinical category of abnormal vibratory and pinprick sensations. Threshold testing showed twice the prevalence of abnormality compared with clinical examination. It is concluded that components of the clinical examination can be identified that, along with quantitative sensory-threshold testing, may provide a satisfactory core assessment for use both in epidemiologic studies and incorporation into more in-depth protocols required for clinical research and practice. The clinical relevance of the greater prevalence of abnormalities on threshold testing will be established by long-term follow-up.