Factors Associated with Higher Pro-Inflammatory Tumor Necrosis Factor-α Levels in Young Women with Type 1 Diabetes.

AIMS: While cytokines play a role in the etiology of type 1 diabetes, cytokines later in the disease are less understood. We therefore investigated associations of pro-inflammatory tumor necrosis factor-α levels measured at prolonged disease duration with C-peptide at diagnosis, long-term glycemic control, diabetes duration, clinical factors, and health behaviors. METHODS: Data and blood were collected during an ancillary study to the longitudinal Wisconsin Diabetes Registry, a population-based cohort followed since diagnosis of type 1 diabetes. The ancillary study was conducted at 13-18 years diabetes duration, and enrolled premenopausal women age 18-45 years (n=87). RESULTS: Higher tumor necrosis factor-α levels at 13-18 years diabetes duration were independently associated with longer duration (p=0.0004) and worse current renal function (p=0.02). Additionally, diabetes duration modified both of the positive associations of tumor necrosis factor-α levels (both interactions p≤0.01) with mean glycemic control during the previous 10 years (significant only in women with longer durations) and current daily caffeine intake (significant only in women with shorter durations). In women with C-peptide measured at diagnosis (n=50), higher tumor necrosis factor-α levels at 13-18 years duration were associated with lower C-peptide (p=0.01), independent of glycemic control during the previous 10 years. CONCLUSIONS: Lower residual C-peptide at diagnosis and poor long-term glycemic control independently predicted higher pro-inflammatory tumor necrosis factor-α levels years later. The novel relationship with C-peptide needs confirmation in a larger cohort. Given the association between tumor necrosis factor-α and diabetes complications, further longitudinal studies may help clarify the potentially complex associations between glycemic control, inflammatory cytokines, and complications.

Poor glycemic control is associated with low BMD detected in premenopausal women with type 1 diabetes.

SUMMARY: The etiology of bone fragility in individuals with type 1 diabetes is unknown. This study demonstrated that bone turnover favors resorption and that poor glycemic control is associated with low bone mineral density (BMD) and low bone turnover, in premenopausal women with type 1 diabetes. The results could inform future interventions. INTRODUCTION: Low BMD and fracture may be complications of type 1 diabetes. We sought to determine the roles of bone turnover and glycemic control in the etiology of low BMD. METHODS: Premenopausal women from the Wisconsin Diabetes Registry Study and matched controls were compared (n = 75 pairs). Heel and forearm BMD were measured, and hip and spine BMD were measured in a subset. Markers of bone formation (osteocalcin) and resorption (NTx), and glycemic control (HbA1c) were determined. RESULTS: Age ranged from 18 to 50 years with a mean of 28, and 97% were Non-Hispanic white. Among women with diabetes, mean disease duration was 16 years and current HbA1c was 8%. Compared to controls, women with diabetes had a high prevalence of previous fracture (37% vs. 24%) and low BMD for age (heel or forearm: 49% vs. 31%), low heel and forearm BMD, and low osteocalcin levels. Levels of NTx were similar, suggesting uncoupled turnover favoring resorption. Poor glycemic control was associated with low BMD at all bone sites except the spine, and with low osteocalcin and NTx levels. CONCLUSIONS: Optimal glycemic control may prevent low BMD and altered bone turnover in type 1 diabetes, and decrease fracture risk.

Risk factors for frequent and severe hypoglycemia in type 1 diabetes.

OBJECTIVE: To determine the risk of frequent and severe hypoglycemia and the associated demographic and clinical risk factors. RESEARCH DESIGN AND METHODS: Demographic and diabetes self-management factors were measured in 415 subjects followed prospectively for 4-6.5 years of type 1 diabetes duration as participants in a population-based incident cohort. Blood samples were collected up to three times yearly to test glycosylated hemoglobin (GHb) levels. Reports of frequent (2-4 times/week) and severe (lost consciousness) hypoglycemia as well as other diabetes self-management data were collected by questionnaires. RESULTS: Frequent hypoglycemia was common (33 and 35% of participants reported this on the 4- and 6.5-year questionnaires, respectively), whereas severe hypoglycemia occurred much less often. Better glycemic control (odds ratio [OR] 1.3 per 2% decrease in GHb, 95% CI 1.1-1.5) and more frequent self-monitored blood glucose (1.5 per blood glucose check, 1.3-1.7) were independently related to frequent hypoglycemia. The association of frequent hypoglycemia with intensive insulin therapy increased with age. Better glycemic control (1.5 per 2% decrease in GHb, 1.2-2.0) and older age were related to severe hypoglycemic reactions. No sociodemographic factors other than age increased the risk of hypoglycemia. CONCLUSIONS: Frequent hypoglycemia was common in a population representing the full range of glycemic control in the community. Intensive insulin management and blood glucose monitoring independently predicted frequent but not severe hypoglycemia. This information may be useful for updating patients such that minor changes in diabetes management might decrease the daily burden of this condition while maintaining intensive insulin therapy.

Risk factors for hospitalization in a cohort with type 1 diabetes. Wisconsin Diabetes Registry.

The authors investigate the postonset hospitalization rate and risk factors during 1987-1994 in Wisconsin, in a population-based, incidence cohort followed from diagnosis of Type 1 diabetes mellitus at ages 0-29 (n = 577). The overall rate was 8.9 +/- 0.60 (standard error) per 100 person-years of diabetes, whereof 5.7 was due to hyperglycemia, 1.9 to hypoglycemia, and 1.3 to other and undetermined causes. Major risk factors for hospitalization were longitudinally measured glycosylated hemoglobin level (rate ratio = 1.5 per 2% increase, 95% confidence interval 1.4-1.7), black/other race (rate ratio = 1.9, 95% confidence interval 1.0-3.6), diagnosis in a non-university-based setting (rate ratio = 1.9, 95% confidence interval 1.2-3.2), female sex (rate ratio = 1.5, 95% confidence interval 1.0-2.4 at age 11), age in males (rate ratio = 0.6, 95% confidence interval 0.4-0.8 per 5-year increase), and public or no insurance up to 18 months postdiagnosis (rate ratio = 2.2, 95% confidence interval 1.1-4.4). For individuals less than 18 years, "black/other race" was replaced in the model by "having other than two biologic parents in the home" (rate ratio = 2.0, 95% confidence interval 1.1-3.5). Hence, hospitalization is common in children, adolescents, and young adults with diabetes, primarily for problems with glycemic control.