Howard H. Moffet

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.

Barriers to Insulin Initiation The Translating Research Into Action for Diabetes Insulin Starts Project

OBJECTIVE Reasons for failing to initiate prescribed insulin (primary nonadherence) are poorly understood. We investigated barriers to insulin initiation following a new prescription. RESEARCH DESIGN AND METHODS We surveyed insulin-naïve patients with poorly controlled type 2 diabetes, already treated with two or more oral agents who were recently prescribed insulin. We compared responses for respondents prescribed, but never initiating, insulin (n = 69) with those dispensed insulin (n = 100). RESULTS Subjects failing to initiate prescribed insulin commonly reported misconceptions regarding insulin risk (35% believed that insulin causes blindness, renal failure, amputations, heart attacks, strokes, or early death), plans to instead work harder on behavioral goals, sense of personal failure, low self-efficacy, injection phobia, hypoglycemia concerns, negative impact on social life and job, inadequate health literacy, health care provider inadequately explaining risks/benefits, and limited insulin self-management training. CONCLUSIONS Primary adherence for insulin may be improved through better provider communication regarding risks, shared decision making, and insulin self-management training.

Missed appointments and poor glycemic control: an opportunity to identify high-risk diabetic patients.

Objective.When patients miss scheduled medical appointments, continuity and effectiveness of healthcare delivery is reduced, appropriate monitoring of health status lapses, and the cost of health services increases. We evaluated the relationship between missed appointments and glycemic control (glycosylated hemoglobin or HbA1c) in a large, managed care population of diabetic patients. Research Design and MethodsMissed appointment rate was related cross-sectionally to glycemic control among 84,040 members of the Kaiser Permanente Northern California Diabetes Registry during 2000. Adjusted least-square mean estimates of HbA1c were derived by level of appointment keeping (none missed, 1–30% missed, and >30% missed appointments for the calendar year) stratified by diabetes therapy. ResultsTwelve percent of the subjects missed more than 30% of scheduled appointments during 2000. Greater rates of missed appointments were associated with significantly poorer glycemic control after adjusting for demographic factors (age, sex), clinical status, and health care utilization. The adjusted mean HbA1c among members who missed >30% of scheduled appointments was 0.70 to 0.79 points higher (P <0.0001) relative to those attending all appointments. Patients who missed more than 30% of their appointments were less likely to practice daily self-monitoring of blood glucose and to have poor oral medication refill adherence. ConclusionPatients who underuse care lack recorded information needed to determine level of risk. Frequently missed appointments were associated with poorer glycemic control and suboptimal diabetes self-management practice, are readily ascertained in clinical settings, and therefore could have clinical utility as a risk-stratifying criterion indicating the need for targeted case management.

Language Barriers, Physician-Patient Language Concordance, and Glycemic Control Among Insured Latinos with Diabetes: The Diabetes Study of Northern California (DISTANCE)

ABSTRACTBACKGROUNDA significant proportion of US Latinos with diabetes have limited English proficiency (LEP). Whether language barriers in health care contribute to poor glycemic control is unknown.OBJECTIVETo assess the association between limited English proficiency (LEP) and glycemic control and whether this association is modified by having a language-concordant physician.DESIGNCross-sectional, observational study using data from the 2005–2006 Diabetes Study of Northern California (DISTANCE). Patients received care in a managed care setting with interpreter services and self-reported their English language ability and the Spanish language ability of their physician. Outcome was poor glycemic control (glycosylated hemoglobin A1c > 9%).KEY RESULTSThe unadjusted percentage of patients with poor glycemic control was similar among Latino patients with LEP (n = 510) and Latino English-speakers (n = 2,683), and higher in both groups than in whites (n = 3,545) (21% vs 18% vs. 10%, p < 0.005). This relationship differed significantly by patient-provider language concordance (p < 0.01 for interaction). LEP patients with language-discordant physicians (n = 115) were more likely than LEP patients with language-concordant physicians (n = 137) to have poor glycemic control (27.8% vs 16.1% p = 0.02). After controlling for potential demographic and clinical confounders, LEP Latinos with language-concordant physicians had similar odds of poor glycemic control as Latino English speakers (OR 0.89; CI 0.53–1.49), whereas LEP Latinos with language-discordant physicians had greater odds of poor control than Latino English speakers (OR 1.76; CI 1.04–2.97). Among LEP Latinos, having a language discordant physician was associated with significantly poorer glycemic control (OR 1.98; CI 1.03–3.80).CONCLUSIONSLanguage barriers contribute to health disparities among Latinos with diabetes. Limited English proficiency is an independent predictor for poor glycemic control among insured US Latinos with diabetes, an association not observed when care is provided by language-concordant physicians. Future research should determine if strategies to increase language-concordant care improve glycemic control among US Latinos with LEP.

Elevated rates of diabetes in Pacific Islanders and Asian subgroups: The Diabetes Study of Northern California (DISTANCE).

OBJECTIVE We estimated the prevalence and incidence of diabetes among specific subgroups of Asians and Pacific Islanders (APIs) in a multiethnic U.S. population with uniform access to care. RESEARCH DESIGN AND METHODS This prospective cohort analysis included 2,123,548 adult members of Kaiser Permanente Northern California, including 1,704,363 with known race/ethnicity (white, 56.9%; Latino, 14.9%; African American, 8.0%; Filipino, 4.9%; Chinese, 4.0%; multiracial, 2.8%; Japanese, 0.9%; Native American, 0.6%; Pacific Islander, 0.5%; South Asian, 0.4%; and Southeast Asian, Korean, and Vietnamese, 0.1% each). We calculated age-standardized (to the 2010 U.S. population) and sex-adjusted diabetes prevalence at baseline and incidence (during the 2010 calendar year). Poisson models were used to estimate relative risks. RESULTS There were 210,632 subjects with prevalent diabetes as of 1 January 2010 and 15,357 incident cases of diabetes identified during 2010. The crude diabetes prevalence was 9.9% and the incidence was 8.0 cases per 1,000 person-years and, after standardizing by age and sex to the 2010 U.S. Census, 8.9% and 7.7 cases per 1,000 person-years. There was considerable variation among the seven largest API subgroups. Pacific Islanders, South Asians, and Filipinos had the highest prevalence (18.3, 15.9, and 16.1%, respectively) and the highest incidence (19.9, 17.2, and 14.7 cases per 1,000 person-years, respectively) of diabetes among all racial/ethnic groups, including minorities traditionally considered high risk (e.g., African Americans, Latinos, and Native Americans). CONCLUSIONS High rates of diabetes among Pacific Islanders, South Asians, and Filipinos are obscured by much lower rates among the large population of Chinese and several smaller Asian subgroups.

New Prescription Medication Gaps: A Comprehensive Measure of Adherence to New Prescriptions

OBJECTIVE Describe a novel approach to comprehensively summarize medication adherence. DATA SOURCES/STUDY SETTING Kaiser Permanente Northern California Diabetes Registry (n approximately 220,000) STUDY DESIGN In a new prescription cohort design (27,329 subjects prescribed new medications), we used pharmacy utilization data to estimate adherence during 24 months follow-up. Proportion of time without sufficient medications (medication gaps) was estimated using a novel measure (New Prescription Medication Gaps [NPMG]) and compared with a traditional measure of adherence. DATA COLLECTION/EXTRACTION METHODS Data derived from electronic medical records and survey responses. PRINCIPAL FINDINGS Twenty-two percent of patients did not become ongoing users (had zero or only one dispensing of the new prescription). The proportion of newly prescribed patients that never became ongoing users was eightfold greater than the proportion who maintained ongoing use, but with inadequate adherence. Four percent of those with at least two dispensings discontinued therapy during the 24 months follow-up. NPMG was significantly associated with high out-of-pocket costs, self-reported adherence, and clinical response to therapy. CONCLUSIONS NPMG is a valid adherence measure. Findings also suggest a larger burden of inadequate adherence than previously thought. Public health efforts have traditionally focused on improving adherence in ongoing users; clearly more attention is needed to address nonpersistence in the very first stages after a new medication is prescribed.

HbA1c and Risk of Severe Hypoglycemia in Type 2 Diabetes: The Diabetes and Aging Study

OBJECTIVE We examined the association between HbA1c level and self-reported severe hypoglycemia in patients with type 2 diabetes. RESEARCH DESIGN AND METHODS Type 2 diabetic patients in a large, integrated healthcare system, who were 30–77 years of age and treated with glucose-lowering therapy, were asked about severe hypoglycemia requiring assistance in the year prior to the Diabetes Study of Northern California survey conducted in 2005–2006 (62% response rate). The main exposure of interest was the last HbA1c level collected in the year preceding the observation period. Poisson regression models adjusted for selected demographic and clinical variables were specified to evaluate the relative risk (RR) of severe hypoglycemia across HbA1c levels. We also tested whether the HbA1c-hypoglycemia association differed across potential effect modifiers (age, diabetes duration, and category of diabetes medication). RESULTS Among 9,094 eligible survey respondents (mean age 59.5 ± 9.8 years, mean HbA1c 7.5 ± 1.5%), 985 (10.8%) reported experiencing severe hypoglycemia. Across HbA1c levels, rates of hypoglycemia were 9.3–13.8%. Compared with those with HbA1c of 7–7.9%, the RR of hypoglycemia was 1.25 (95% CI 0.99–1.57), 1.01 (0.87–1.18), 0.99 (0.82–1.20), and 1.16 (0.97–1.38) among those with HbA1c <6, 6–6.9, 8–8.9, and ≥9%, respectively, in a fully adjusted model. Age, diabetes duration, and category of diabetes medication did not significantly modify the HbA1c-hypoglycemia relationship. CONCLUSIONS Severe hypoglycemia was common among patients with type 2 diabetes across all levels of glycemic control. Risk tended to be higher in patients with either near-normal glycemia or very poor glycemic control.

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.

Pioglitazone initiation and subsequent hospitalization for congestive heart failure.

Aims  Thiazolidinediones (TZD) have been associated with an expansion in plasma volume and the development of peripheral oedema. A recent study reported an association between the use of TZDs and development of congestive heart failure (CHF). The objective of this study was to determine if short‐term use of pioglitazone, a TZD, is associated with increased risk of admission to hospital because of CHF in a well‐characterized, community‐based cohort of Type 2 diabetic patients without prevalent CHF.