Permanente Northern California Diabetes Registry Research Articles

Willingness to take less medication for type 2 diabetes among older patients: The Diabetes & Aging Study.

To examine the willingness of older patients to take less diabetes medication (de-intensify) and to identify characteristics associated with willingness to de-intensify treatment. Survey conducted in 2019 in an age-stratified, random sample of older (65-100 years) adults with diabetes on glucose-lowering medications in the Kaiser Permanente Northern California Diabetes Registry. We classified survey responses to the question: "I would be willing to take less medication for my diabetes" as willing, neutral, or unwilling to de-intensify. Willingness to de-intensify treatment was examined by several clinical characteristics, including American Diabetes Association (ADA) health status categories used for individualizing glycemic targets. Analyses were weighted to account for over-sampling of older individuals. A total of 1337 older adults on glucose-lowering medication(s) were included (age 74.2 ± 6.0 years, 44% female, 54.4% non-Hispanic white). The proportions of participants willing, neutral, or unwilling to take less medication were 51.2%, 27.3%, and 21.5%, respectively. Proportions of willing to take less medication varied by age (65-74 years: 54.2% vs. 85+ years: 38.5%) and duration of diabetes (0-4 years: 61.0% vs. 15+ years: 44.2%), both p < 0.001. Patients on 1-2 medications were more willing to take less medication(s) compared with patients on 10+ medications (62.1% vs. 46.6%, p = 0.03). Similar proportions of willingness to take less medications were seen across ADA health status, and HbA1c. Willingness to take less medication(s) was similar across survey responses to questions about patient-clinician relationships. Clinical guidelines suggest considering treatment de-intensification in older patients with longer duration of diabetes, yet patients with these characteristics are less likely to be willing to take less medication(s).

Development and Validation of a Diabetic Retinopathy Risk Stratification Algorithm.

Although diabetic retinopathy is a leading cause of blindness worldwide, diabetes-related blindness can be prevented through effective screening, detection, and treatment of disease. The study goal was to develop risk stratification algorithms for the onset of retinal complications of diabetes, including proliferative diabetic retinopathy, referable retinopathy, and macular edema. Retrospective cohort analysis of patients from the Kaiser Permanente Northern California Diabetes Registry who had no evidence of diabetic retinopathy at a baseline diabetic retinopathy screening during 2008-2020 was performed. Machine learning and logistic regression prediction models for onset of proliferative diabetic retinopathy, diabetic macular edema, and referable retinopathy detected through routine screening were trained and internally validated. Model performance was assessed using area under the curve (AUC) metrics. The study cohort (N = 276,794) was 51.9% male and 42.1% White. Mean (±SD) age at baseline was 60.0 (±13.1) years. A machine learning XGBoost algorithm was effective in identifying patients who developed proliferative diabetic retinopathy (AUC 0.86; 95% CI, 0.86-0.87), diabetic macular edema (AUC 0.76; 95% CI, 0.75-0.77), and referable retinopathy (AUC 0.78; 95% CI, 0.78-0.79). Similar results were found using a simpler nine-covariate logistic regression model: proliferative diabetic retinopathy (AUC 0.82; 95% CI, 0.80-0.83), diabetic macular edema (AUC 0.73; 95% CI, 0.72-0.74), and referable retinopathy (AUC 0.75; 95% CI, 0.75-0.76). Relatively simple logistic regression models using nine readily available clinical variables can be used to rank order patients for onset of diabetic eye disease and thereby more efficiently prioritize and target screening for at risk patients.

Use and Discontinuation of Insulin Treatment Among Adults Aged 75 to 79 Years With Type 2 Diabetes

Among older individuals with type 2 diabetes, those with poor health have greater risk and derive less benefit from tight glycemic control with insulin. To examine whether insulin treatment is used less frequently and discontinued more often among older individuals with poor health compared with those in good health. This longitudinal cohort study included 21 531 individuals with type 2 diabetes followed for up to 4 years starting at age 75 years. Electronic health record data from the Kaiser Permanente Northern California Diabetes Registry was collected to characterize insulin treatment and glycemic control over time. Data were collected from January 1, 2009, through December 31, 2017, and analyzed from February 2, 2018, through June 30, 2019. Health status was defined as good (<2 comorbid conditions or 2 comorbidities but physically active), intermediate (>2 comorbidities or 2 comorbidities and no self-reported weekly exercise), or poor (having end-stage pulmonary, cardiac, or renal disease; diagnosis of dementia; or metastatic cancer). Insulin use prevalence at age 75 years and discontinuation among insulin users over the next 4 years (or 6 months prior to death if <4 years). Of 21 531 patients, 10 396 (48.3%) were women, and the mean (SD) age was 75 (0) years. Nearly one-fifth of 75-year-olds (4076 [18.9%]) used insulin. Prevalence and adjusted risk ratios (aRRs) of insulin use at age 75 years were higher in individuals with poor health (29.4%; aRR, 2.03; 95% CI, 1.87-2.20; P < .01) and intermediate health (27.5%; aRR, 1.85; 95% CI, 1.74-1.97; P < .01) relative to good health (10.5% [reference]). One-third (1335 of 4076 [32.7%]) of insulin users at age 75 years discontinued insulin within 4 years of cohort entry (and at least 6 months prior to death). Likelihood of continued insulin use was higher among individuals in poor health (aRR, 1.47; 95% CI, 1.27-1.67; P < .01) and intermediate health (aRR, 1.16; 95% CI, 1.05-1.30; P < .01) compared with good health (reference). These same prevalence and discontinuation patterns were present in the subset with tight glycemic control (hemoglobin A1c <7.0%). In older individuals with type 2 diabetes, insulin use was most prevalent among those in poor health, whereas subsequent insulin discontinuation after age 75 years was most likely in healthier patients. Changes are needed in current practice to better align with guidelines that recommend reducing treatment intensity as health status declines.

Association Between Neighborhood Supermarket Presence and Glycated Hemoglobin Levels Among Patients With Type 2 Diabetes Mellitus.

We estimated associations between neighborhood supermarket gain or loss and glycemic control (assessed by glycated hemoglobin (HbA1c) values) in patients from the Kaiser Permanente Northern California Diabetes Registry (n=434,806 person-years; 2007-2010). Annual clinical measures were linked to metrics from a geographic information system for each patient's address of longest residence. We estimated the association between change in supermarket presence (gain, loss, or no change) and change in HbA1c value, adjusting for individual- and area-level attributes and according to baseline glycemic control (near normal, <6.5%; good, 6.5%-7.9%; moderate, 8.0%-8.9%; and poor, ≥9.0%). Supermarket loss was associated with worse HbA1c trajectories for those with good, moderate, and poor glycemic control at baseline, while supermarket gain was associated with marginally better HbA1c outcomes only among patients with near normal HbA1c values at baseline. Patients with the poorest baseline HbA1c values (≥9.0%) had the worst associated changes in glycemic control following either supermarket loss or gain. Differences were not clinically meaningful relative to no change in supermarket presence. For patients with type 2 diabetes mellitus, gaining neighborhood supermarket presence did not benefit glycemic control in a substantive way. The significance of supermarket changes on health depends on a complex interaction of resident, neighborhood, and store characteristics.

Is a reduction in distance to nearest supermarket associated with BMI change among type 2 diabetes patients?

We examined whether residing within 2 miles of a new supermarket opening was longitudinally associated with a change in body mass index (BMI). We identified 12 new supermarkets that opened between 2009 and 2010 in 8 neighborhoods. Using the Kaiser Permanente Northern California Diabetes Registry, we identified members with type 2 diabetes residing continuously in any of these neighborhoods 12 months prior to the first supermarket opening until 10 months following the opening of the last supermarket. Exposure was defined as a reduction (yes/no) in travel distance to the nearest supermarket as a result of a new supermarket opening. First difference regression models were used to estimate the impact of reduced supermarket distance on BMI, adjusting for longitudinal changes in patient and neighborhood characteristics. Among patients in the exposed group, new supermarket openings reduced travel distance to the nearest supermarket by 0.7 miles on average. However, reduced distance to nearest supermarket was not associated with BMI changes. Overall, we found no evidence that reduced supermarket distance was associated with reduced levels of obesity for residents with type 2 diabetes.

Low socioeconomic status is associated with increased risk for hypoglycemia in diabetes patients: the Diabetes Study of Northern California (DISTANCE).

Social risk factors for hypoglycemia are not well understood. Cross-sectional analysis from the DISTANCE study, a multi-language, ethnically-stratified random sample of adults in the Kaiser Permanente Northern California diabetes registry, conducted in 2005-2006 (response rate 62%). Exposures were income and educational attainment; outcome was patient report of severe hypoglycemia. To test the association, we used multivariable logistic regression to adjust for demographic and clinical factors. 14,357 patients were included. Reports of severe hypoglycemia were common (11%), and higher in low-income vs. high-income (16% vs. 8.8) and low-education vs. high-education (11.9% vs. 8.9%) groups. In multivariable analysis, incomes of less than $15,000 (OR 1.51 95%CI 1.19-1.91), $15,000-$24,999 (OR 1.57 95%CI 1.27-1.94), and high school or less education (OR 1.42, 95% CI 1.24-1.63) were associated with increased hypoglycemia, similar to insulin use (OR 1.44 95%CI 1.19-1.74). Low income and educational attainment are important risk factors for hypoglycemia.

Racial/Ethnic Differences in Dementia Risk Among Older Type 2 Diabetic Patients: The Diabetes and Aging Study

OBJECTIVEAlthough patients with type 2 diabetes have double the risk of dementia, potential racial/ethnic differences in dementia risk have not been explored in this population. We evaluated racial/ethnic differences in dementia and potential explanatory factors among older diabetic patients.RESEARCH DESIGN AND METHODSWe identified 22,171 diabetic patients without preexisting dementia aged ≥60 years (14,546 non-Hispanic whites, 2,484 African Americans, 2,363 Latinos, 2,262 Asians, 516 Native Americans) from the Kaiser Permanente Northern California Diabetes Registry. We abstracted prevalent medical history (1 January 1996 to 31 December 1997) and dementia incidence (1 January 1998 to 31 December 2007) from medical records and calculated age-adjusted incidence densities. We fit Cox proportional hazards models adjusted for age, sex, education, diabetes duration, and markers of clinical control.RESULTSDementia was diagnosed in 3,796 (17.1%) patients. Age-adjusted dementia incidence densities were highest among Native Americans (34/1,000 person-years) and African Americans (27/1,000 person-years) and lowest among Asians (19/1,000 person-years). In the fully adjusted model, hazard ratios (95% CIs) (relative to Asians) were 1.64 (1.30–2.06) for Native Americans, 1.44 (1.24–1.67) for African Americans, 1.30 (1.15–1.47) for non-Hispanic whites, and 1.19 (1.02–1.40) for Latinos. Adjustment for diabetes-related complications and neighborhood deprivation index did not change the results.CONCLUSIONSAmong type 2 diabetic patients followed for 10 years, African Americans and Native Americans had a 40–60% greater risk of dementia compared with Asians, and risk was intermediate for non-Hispanic whites and Latinos. Adjustment for sociodemographics, diabetes-related complications, and markers of clinical control did not explain observed differences. Future studies should investigate why these differences exist and ways to reduce them.

Hypoglycemia in Diabetes Common Across Glycemic Control Levels

Hypoglycemia is common among patients being treated for type 2 diabetes, regardless of their level of glycemic control, according to findings from the Diabetes Study of Northern California (DISTANCE) survey. The findings challenge the conventional wisdom that hypoglycemia occurs only among those with the lowest hemoglobin A1c levels, reported Dr. Kasia J. Lipska of Yale University, New Haven, Conn., and colleagues. The study was published in Diabetes Care (2013;36:3535-42). Among 9,094 adults with diabetes who participated in the survey, 11% reported experiencing severe hypoglycemia in the past year, with nearly 1 in 4 (24%) reporting more than three events during that time period. In an unadjusted analysis, those with HbA at the highest and lowest levels were most likely to experience hypoglycemia, the investigators said. Compared with those with “good” HbA levels of 7.0%-7.9%; the relative risk of hypoglycemia was 1.25 in those with “near normal” levels of less than 6%, 1.01 in those with “very good” levels of 6.0%-6.9%, 0.99 in those with “suboptimal” levels of 8.0%-8.9%, and 1.16 among those with “very poor” levels of 9% or greater, they explained. However, the elevated relative risk was statistically significant only for those with HbA of 9% or greater, they noted, adding that while adjustment for demographic variables did not “alter the shape of the relationship,” and while the point estimates for hypoglycemia risk remained higher at the two extremes of glycemic control, the differences in risk between each HbA category and the reference group did not differ significantly in the fully adjusted model. Study participants were patients with type 2 diabetes aged 30-77 years, who were members of the Kaiser Permanente Northern California Diabetes Registry. The patients, who were using glucose-lowering therapy, were surveyed during 2005-2006 about episodes of severe hypoglycemia, such as episodes during which they passed out or required medical assistance. Patients most likely to report hypoglycemic episodes were women; those taking more than four medications for chronic conditions; those using either insulin or a secretagogue during the pre-observation period; and those with longer duration of disease, prior history of hypoglycemia, and multiple comorbidities, the investigators noted. After examining the prevalence of hypoglycemia across potential effect modifiers, however, they found no significant interaction. Prior studies have resulted in inconsistent findings about the relationship between glucose control and hypoglycemic events, but findings from the current study suggest that “hypoglycemia occurs across all levels of HbA, with higher risk associated with near-normal or very poor glycemic control,” the investigators said. The findings are important, they said, because several studies have shown that patients who experience severe hypoglycemia are at increased risk for a number of unfavorable health outcomes, including dementia, falls, fall-related fractures, cardiovascular events, poor health–related quality of life, and increased mortality. The researchers noted that in addition to efforts to limit adverse effects of overtreatment and to improve patient outcomes, efforts to consider the safety of the various glucose-lowering therapies in patients with higher HbA levels are needed. “Poorly controlled diabetes appears to be associated with both higher risk of diabetic complications and higher risk of treatment-related hypoglycemia. Therefore, quality improvement efforts must balance the need to improve glucose levels with safety of antihyperglycemic therapy in this group,” they said. Though limited by a number of factors, including self-reporting of hypoglycemia without laboratory confirmation and a wide age range of participants, which limits applicability to elderly patients with diabetes, the findings in this usual-care setting nonetheless underscore the importance of directing efforts to improve the safety of glucose-lowering therapies. Such efforts must be directed not only to patients achieving intensive glucose control, but also to those with poorly controlled disease, the investigators concluded, noting that “future analyses are needed to identify management strategies and treatment factors that may mitigate hypoglycemia risk.” The DISTANCE survey was funded by numerous grants, including grants to individual authors or their employers from the National Institute on Aging and the National Heart, Lung, and Blood Institute.

Abstract 2274: Metformin use and risk of lung cancer in patients with diabetes.

Abstract Observational studies suggest that cancer incidence is lower in patients with type 2 diabetes treated with metformin, relative to patients treated with other diabetes medications. The few studies to examine metformin use in relation to lung cancer risk, however, have produced inconsistent results. To clarify this relationship, we conducted a retrospective cohort study of 50,722 adults aged 40 years or older included in the Kaiser Permanente Northern California Diabetes Registry, who completed a mailed survey administered in 1994 to 1996 on health-related traits and behaviors. All prescribed diabetes medications were identified for each patient from pharmacy records. Patients were followed for lung cancer from 1997 to 2009, with a median follow-up of 8.1 years. Using Cox regression, with age as the time scale, rate ratios (RR) and 95% confidence intervals (CI) were calculated to estimate risk of lung cancer associated with new use of metformin, adjusted for sex, race/ethnicity, smoking status, income, education level, diabetes duration, baseline measures of hemoglobin A1c and creatinine, and ever use of other types of diabetes medications. Measures of metformin use, along with ever use for each type of diabetes medication, were modeled as time-dependent variables. During 389,887 person-years of follow-up, 685 patients were diagnosed with lung cancer. The adjusted RR for ever use of metformin was 0.95 (95% CI, 0.79-1.14). For duration of metformin use, the adjusted RRs for &amp;lt;2.0, 2.0-4.9, and 5.0+ years were 1.01 (95% CI, 0.80-1.28), 0.94 (95% CI, 0.73-1.22), and 0.86 (95% CI, 0.63-1.18), respectively. In analyses stratified by smoking status, the adjusted RRs for ever use of metformin were 0.98 (95% CI, 0.79-1.21) in ever smokers and 0.59 (95% CI, 0.34-1.01) in never smokers. However, in never smokers, the number of users diagnosed with lung cancer was relatively small, and no dose-response decrease in risk with increasing duration of metformin use was found; the corresponding adjusted RRs for &amp;lt;2.0, 2.0-4.9, and 5.0+ years of metformin use were 0.52 (95% CI, 0.23-1.16), 0.58 (95% CI, 0.26-1.26), and 0.70 (95% CI, 0.31-1.58), respectively. Our results suggest that metformin use is not associated with lung cancer risk in former or current smokers with diabetes. Additional research is needed to determine whether metformin use might alter lung cancer risk in never smokers with diabetes. Citation Format: Lori C. Sakoda, Ninah S. Achacoso, Charles P. Quesenberry, Tiffany Peng, Samantha F. Ehrlich, Assiamira Ferrara, Laurel A. Habel. Metformin use and risk of lung cancer in patients with diabetes. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 2274. doi:10.1158/1538-7445.AM2013-2274

Increased cancer risk with drug use among patients with diabetes: Are the biased methods the culprit?

Increased cancer risk with drug use among patients with diabetes: Are the biased methods the culprit?

Comment: Analyses Using Time-Dependent Pioglitazone Usage in Cox Models May Lead to Wrong Conclusions About Its Association With Cancer

We read the two articles published in a recent issue of Diabetes Care by Lewis et al. (1) and Ferrara et al. (2) with interest. The first study tested a time-dependent use of pioglitazone for the risk of bladder cancer among 193,099 diabetic patients in the Kaiser Permanente Northern California Diabetes Registry and concluded that use of the drug over 24 months was associated with an increased risk of bladder cancer (hazard ratio 1.4, 95% CI 1.03–2.0). The second study tested a time-dependent use of pioglitazone for the risk of cancer among 252,467 diabetic patients aged ≥40 years from the Kaiser Permanente Northern California Diabetes Registry and found that ever use of pioglitazone was not …

Cohort Study of Pioglitazone and Cancer Incidence in Patients With Diabetes

OBJECTIVETo explore whether treatment with pioglitazone was associated with risk of incident cancer at the 10 most common sites (prostate, female breast, lung/bronchus, endometrial, colon, non-Hodgkin lymphoma [NHL], pancreas, kidney/renal pelvis, rectal, and melanoma).RESEARCH DESIGN AND METHODSA cohort study of 252,467 patients aged ≥40 years from the Kaiser Permanente Northern California Diabetes Registry was conducted. All prescriptions for diabetes medications were identified by pharmacy records. Cox proportional hazards models were used to examine the association between risk of incident cancer and ever use, duration, dose, and time since initiation of pioglitazone (modeled as time-dependent variables).RESULTSIn models adjusted for age, sex, year of cohort entry, race/ethnicity, income, smoking, glycemic control, diabetes duration, creatinine levels, congestive heart failure, and use of other diabetes medications, the hazard ratio (HR) for each cancer associated with ever use of pioglitazone ranged from 0.7 to 1.3, with all 95% CIs including 1.0. There was a suggestion of an increased risk of melanoma (HR 1.3 [95% CI 0.9–2.0]) and NHL (1.3 [1.0–1.8]) and a decreased risk of kidney/renal pelvis cancers (0.7 [0.4–1.1]) associated with ever use of pioglitazone. These associations were unaltered with increasing dose, duration, or time since first use.CONCLUSIONSWe found no clear evidence of an association between use of pioglitazone and risk of the incident cancers examined. Because the maximum duration of follow-up was fewer than 6 years after the initiation of pioglitazone, longer-term studies are needed.

Risk of Bladder Cancer Among Diabetic Patients Treated With Pioglitazone

OBJECTIVESome preclinical in vivo studies and limited human data suggest a possible increased risk of bladder cancer with pioglitazone therapy. This is an interim report of an ongoing cohort study examining the association between pioglitazone therapy and the risk of bladder cancer in patients with diabetes.RESEARCH DESIGN AND METHODSThis study includes 193,099 patients in the Kaiser Permanente Northern California diabetes registry who were ≥40 years of age between 1997 and 2002. Those with prior bladder cancer were excluded. Ever use of each diabetes medication (defined as two or more prescriptions within 6 months) was treated as a time-dependent variable. Cox regression–generated hazard ratios (HRs) compared pioglitazone use with nonpioglitazone use adjusted for age, sex, race/ethnicity, diabetes medications, A1C, heart failure, household income, renal function, other bladder conditions, and smoking.RESULTSThe group treated with pioglitazone comprised 30,173 patients. There were 90 cases of bladder cancer among pioglitazone users and 791 cases of bladder cancer among nonpioglitazone users. Overall, ever use of pioglitazone was not associated with risk of bladder cancer (HR 1.2 [95% CI 0.9–1.5]), with similar results in men and women (test for interaction P = 0.8). However, in the a priori category of >24 months of therapy, there was an increased risk (1.4 [1.03–2.0]). Ninety-five percent of cancers diagnosed among pioglitazone users were detected at early stage.CONCLUSIONSIn this cohort of patients with diabetes, short-term use of pioglitazone was not associated with an increased incidence of bladder cancer, but use for more than 2 years was weakly associated with increased risk.

Heterogeneity of Diabetes Outcomes Among Asians and Pacific Islanders in the U.S.

OBJECTIVEEthnic minorities with diabetes typically have lower rates of cardiovascular outcomes and higher rates of end-stage renal disease (ESRD) compared with whites. Diabetes outcomes among Asian and Pacific Islander subgroups have not been disaggregated.RESEARCH DESIGN AND METHODSWe performed a prospective cohort study (1996–2006) of patients enrolled in the Kaiser Permanente Northern California Diabetes Registry. There were 64,211 diabetic patients, including whites (n = 40,286), blacks (n = 8,668), Latinos (n = 7,763), Filipinos (n = 3,572), Chinese (n = 1,823), Japanese (n = 951), Pacific Islanders (n = 593), and South Asians (n = 555), enrolled in the registry. We calculated incidence rates (means ± SD; 7.2 ± 3.3 years follow-up) and created Cox proportional hazards models adjusted for age, educational attainment, English proficiency, neighborhood deprivation, BMI, smoking, alcohol use, exercise, medication adherence, type and duration of diabetes, HbA1c, hypertension, estimated glomerular filtration rate, albuminuria, and LDL cholesterol. Incidence of myocardial infarction (MI), congestive heart failure, stroke, ESRD, and lower-extremity amputation (LEA) were age and sex adjusted.RESULTSPacific Islander women had the highest incidence of MI, whereas other ethnicities had significantly lower rates of MI than whites. Most nonwhite groups had higher rates of ESRD than whites. Asians had ~60% lower incidence of LEA compared with whites, African Americans, or Pacific Islanders. Incidence rates in Chinese, Japanese, and Filipinos were similar for most complications. For the three macrovascular complications, Pacific Islanders and South Asians had rates similar to whites.CONCLUSIONSIncidence of complications varied dramatically among the Asian subgroups and highlights the value of a more nuanced ethnic stratification for public health surveillance and etiologic research.

Advances in Vascular Cognitive Impairment

Advances in Vascular Cognitive Impairment

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

Describe a novel approach to comprehensively summarize medication adherence. Kaiser Permanente Northern California Diabetes Registry (n approximately 220,000) 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 derived from electronic medical records and survey responses. 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. 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.

The Relationship Between Alcohol Consumption and Glycemic Control Among Patients with Diabetes: The Kaiser Permanente Northern California Diabetes Registry

Alcohol consumption is a common behavior. Little is known about the relationship between alcohol consumption and glycemic control among people with diabetes. To evaluate the association between alcohol consumption and glycemic control. Survey follow-up study, 1994-1997, among Kaiser Permanente Northern California members. 38,564 adult diabetes patients. Self-reported alcohol consumption, and hemoglobin A1C (A1C), assessed within 1 year of survey date. Linear regression of A1C by alcohol consumption was performed, adjusted for sociodemographic variables, clinical variables, and diabetes disease severity. Least squares means estimates were derived. In multivariate-adjusted models, A1C values were 8.88 (lifetime abstainers), 8.79 (former drinkers), 8.90 (<0.1 drink/day), 8.71 (0.1-0.9 drink/day), 8.51 (1-1.9 drinks/day), 8.39 (2-2.9 drinks/day), and 8.47 (>/=3 drinks/day). Alcohol consumption was linearly (p < 0.001) and inversely (p = 0.001) associated with A1C among diabetes patients. Alcohol consumption is inversely associated with glycemic control among diabetes patients. This supports current clinical guidelines for moderate levels of alcohol consumption among diabetes patients. As glycemic control affects incidence of complications of diabetes, the lower A1C levels associated with moderate alcohol consumption may translate into lower risk for complications.

Pioglitazone initiation and subsequent hospitalization for congestive heart failure

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. A cohort study of all patients in the Kaiser Permanente Medical Care Program with Type 2 diabetes (Kaiser Permanente Northern California Diabetes Registry) who initiated any diabetes pharmacotherapy (n = 23 440) between October 1999 and November 2001. Only patients initiating single new therapies ('new users') were included to reduce confounding and create mutually exclusive exposure groups. We constructed Cox proportional hazards models (with sulphonylureas initiators specified as the reference group) to evaluate the impact of initiating new diabetes therapies on time-to-incident admission to hospital because of CHF, defined by primary hospital discharge diagnosis. Patients initiated pioglitazone (15.2%), sulphonylureas (25.3%), metformin (50.9%), and insulin (8.6%) alone, or as additions to pre-existing or maintained therapies. Three hundred and twenty admissions for CHF were observed during the follow-up (mean 10.2 months) after drug initiation. Relative to patients initiating sulphonylureas, there were no significant increases in the incidence of hospitalization for CHF in those initiating pioglitazone [hazard ratio (HR) = 1.28; 95% confidence interval (CI): 0.85-1.92] after adjusting for demographic, behavioural and clinical factors. There was a significantly higher incidence among those initiating insulin (HR = 1.56; 95% CI: 1.00-2.45) and lower incidence among those initiating metformin (HR = 0.70; 95% CI: 0.49-0.99). This study of patients with Type 2 diabetes failed to find evidence that short-term pioglitazone use was associated with an elevated risk of hospitalization for CHF relative to the standard, first-line diabetes therapy.

Missed Appointments and Poor Glycemic Control

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. Missed 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. Twelve 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. Patients 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.