Priya M. John

Rates of Complications and Mortality in Older Patients With Diabetes Mellitus: The Diabetes and Aging Study

IMPORTANCE In the coming decades, the population of older adults with type 2 diabetes mellitus is expected to grow substantially. Understanding the clinical course of diabetes in this population is critical for establishing evidence-based clinical practice recommendations, identifying research priorities, allocating resources, and setting health care policies. OBJECTIVE To contrast the rates of diabetes complications and mortality across age and diabetes duration categories. DESIGN, SETTING, AND PARTICIPANTS This cohort study (2004-2010) included 72,310 older (≥ 60 years) patients with type 2 diabetes enrolled in a large, integrated health care delivery system. Incidence densities (events per 1000 person-years) were calculated for each age category (60-69, 70-79, and ≥ 80 years) and duration of diabetes (shorter [0-9 years] vs longer [≥ 10 years]). MAIN OUTCOMES AND MEASURES Incident acute hyperglycemic events, acute hypoglycemic events (hypoglycemia), microvascular complications (end-stage renal disease, peripheral vascular disease, lower limb amputation, and diabetic eye disease), cardiovascular complications (coronary artery disease, cerebrovascular disease, and congestive heart failure), and all-cause mortality. RESULTS Among older adults with diabetes of short duration, cardiovascular complications followed by hypoglycemia were the most common nonfatal complications. For example, among individuals aged 70 to 79 years with a short duration of diabetes, coronary artery disease and hypoglycemia rates were higher (11.47 per 1000 person-years and 5.03 per 1000 person-years, respectively) compared with end-stage renal disease (2.60 per 1000 person-years), lower limb amputation (1.28 per 1000 person-years), and acute hyperglycemic events (0.82 per 1000 person-years). We observed a similar pattern among patients in the same age group with a long duration of diabetes, with some of the highest incidence rates in coronary artery disease and hypoglycemia (18.98 per 1000 person-years and 15.88 per 1000 person-years, respectively) compared with end-stage renal disease (7.64 per 1000 person-years), lower limb amputation (4.26 per 1000 person-years), and acute hyperglycemic events (1.76 per 1000 person-years). For a given age group, the rates of each outcome, particularly hypoglycemia and microvascular complications, increased dramatically with longer duration of the disease. However, for a given duration of diabetes, rates of hypoglycemia, cardiovascular complications, and mortality increased steeply with advancing age, and rates of microvascular complications remained stable or declined. CONCLUSIONS AND RELEVANCE Duration of diabetes and advancing age independently predict diabetes morbidity and mortality rates. As long-term survivorship with diabetes increases and as the population ages, more research and public health efforts to reduce hypoglycemia will be needed to complement ongoing efforts to reduce cardiovascular and microvascular complications.

Glycemic Control, Complications, and Death in Older Diabetic Patients: The Diabetes and Aging Study

OBJECTIVE To identify the range of glycemic levels associated with the lowest rates of complications and mortality in older diabetic patients. RESEARCH DESIGN AND METHODS We conducted a retrospective cohort study (2004–2008) of 71,092 patients with type 2 diabetes, aged ≥60 years, enrolled in Kaiser Permanente Northern California. We specified Cox proportional hazards models to evaluate the relationships between baseline glycated hemoglobin (A1C) and subsequent outcomes (nonfatal complications [acute metabolic, microvascular, and cardiovascular events] and mortality). RESULTS The cohort (aged 71.0 ± 7.4 years [means ± SD]) had a mean A1C of 7.0 ± 1.2%. The risk of any nonfatal complication rose monotonically for levels of A1C >6.0% (e.g., adjusted hazard ratio 1.09 [95% CI 1.02–1.16] for A1C 6.0–6.9% and 1.86 [1.63–2.13] for A1C ≥11.0%). Mortality had a U-shaped relationship with A1C. Compared with the risk with A1C <6.0%, mortality risk was lower for A1C levels between 6.0 and 9.0% (e.g., 0.83 [0.76–0.90] for A1C 7.0–7.9%) and higher at A1C ≥11.0% (1.31 [1.09–1.57]). Risk of any end point (complication or death) became significantly higher at A1C ≥8.0%. Patterns generally were consistent across age-groups (60–69, 70–79, and ≥80 years). CONCLUSIONS Observed relationships between A1C and combined end points support setting a target of A1C <8.0% for older patients, with the caution that A1Cs <6.0% were associated with increased mortality risk. Additional research is needed to evaluate the low A1C–mortality relationship, as well as protocols for individualizing diabetes care.

Correlates of Quality of Life in Older Adults With Diabetes: The Diabetes & Aging Study

OBJECTIVE To evaluate associations between health-related quality of life (HRQL) and geriatric syndromes, diabetes complications, and hypoglycemia in older adults with diabetes. RESEARCH DESIGN AND METHODS A race-stratified random sample of 6,317 adults with type 2 or type 1 diabetes, aged 60 to 75 years, enrolled in Kaiser Permanente Northern California, who completed a survey that included a HRQL instrument based on the Short Form 8-item health survey. Administrative records were used to ascertain diagnoses of geriatric syndromes, diabetes complications, and hypoglycemia. Associations were estimated between HRQL and exposures in exposure-specific and combined exposure models (any syndrome, any complication, or hypoglycemia). Conservatively, differences of ≥3 points were considered the minimally important difference in HRQL scores. RESULTS HRQL was lower with nearly all exposures of interest. The lowest physical HRQL was associated with amputation. In combined exposure models, geriatric syndromes (−5.3 [95% CI −5.8 to −4.8], P < 0.001) and diabetes complications (−3.5 [−4.0 to −2.9], P < 0.001) were associated with lower physical HRQL. The lowest mental HRQL was associated with depression, underweight (BMI <18 kg/m2), amputation, and hypoglycemia. In combined exposure models, only hypoglycemia was associated with lower mental HRQL (−4.0 [−7.0 to −1.1], P = 0.008). CONCLUSIONS Geriatric syndromes and hypoglycemia are associated with lower HRQL to a comparable degree as diabetes complications. Addressing geriatric syndromes and avoiding hypoglycemia should be given as high a priority as preventing diabetes complications in older adults with diabetes.

The Cost-Effectiveness of Continuous Glucose Monitoring in Type 1 Diabetes

OBJECTIVE Continuous glucose monitoring (CGM) has been found to improve glucose control in type 1 diabetic patients. We estimated the cost-effectiveness of CGM versus standard glucose monitoring in type 1 diabetes. RESEARCH DESIGN AND METHODS This societal cost-effectiveness analysis (CEA) was conducted in trial populations in which CGM has produced a significant glycemic benefit (A1C ≥7.0% in a cohort of adults aged ≥25 years and A1C <7.0% in a cohort of all ages). Trial data were integrated into a simulation model of type 1 diabetes complications. The main outcome was the cost per quality-adjusted life-year (QALY) gained. RESULTS During the trials, CGM patients experienced an immediate quality-of-life benefit (A1C ≥7.0% cohort: 0.70 quality-adjusted life-weeks [QALWs], P = 0.49; A1C <7.0% cohort: 1.39 QALWs, P = 0.04) and improved glucose control. In the long-term, CEA for the A1C ≥7.0% cohort, CGM was projected to reduce the lifetime probability of microvascular complications; the average gain in QALYs was 0.60. The incremental cost-effectiveness ratio (ICER) was

The Cost-Effectiveness of Personalized Genetic Medicine The case of genetic testing in neonatal diabetes

98,679/QALY (95% CI −60,000 [fourth quadrant] to −87,000 [second quadrant]). For the A1C <7.0% cohort, the average gain in QALYs was 1.11. The ICER was

Cost-Effectiveness of MODY Genetic Testing: Translating Genomic Advances Into Practical Health Applications

78,943/QALY (15,000 [first quadrant] to −291,000 [second quadrant]). If the benefit of CGM had been limited to the long-term effects of improved glucose control, the ICER would exceed

Public Health Implications of Recommendations to Individualize Glycemic Targets in Adults With Diabetes

700,000/QALY. If test strip use had been two per day with CGM long term the ICER for CGM would improve significantly. CONCLUSIONS Long-term projections indicate that CGM is cost-effective among type 1 diabetic patients at the

Health utilities for children and adults with type 1 diabetes.

100,000/QALY threshold, although considerable uncertainty surrounds these estimates.

Association Between Estimated GFR, Health-Related Quality of Life, and Depression Among Older Adults With Diabetes: The Diabetes and Aging Study

OBJECTIVE Neonatal diabetes mellitus is a rare form of diabetes diagnosed in infancy. Nearly half of patients with permanent neonatal diabetes have mutations in the genes for the ATP-sensitive potassium channel (KCNJ11 and ABCC8) that allow switching from insulin to sulfonylurea therapy. Although treatment conversion has dramatic benefits, the cost-effectiveness of routine genetic testing is unknown. RESEARCH DESIGN AND METHODS We conducted a societal cost-utility analysis comparing a policy of routine genetic testing to no testing among children with permanent neonatal diabetes. We used a simulation model of type 1 diabetic complications, with the outcome of interest being the incremental cost-effectiveness ratio (ICER,

Classification of Older Adults Who Have Diabetes by Comorbid Conditions, United States, 2005–2006

/quality-adjusted life-year [QALY] gained) over 30 years of follow-up. RESULTS In the base case, the testing policy dominated the no-testing policy. The testing policy was projected to bring about quality-of-life benefits that enlarged over time (0.32 QALYs at 10 years, 0.70 at 30 years) and produced savings in total costs that were present as early as 10 years (