Charles M. Alexander

Diabetes mellitus, impaired fasting glucose, atherosclerotic risk factors, and prevalence of coronary heart disease

Patients with diabetes mellitus (DM), both diagnosed (history of) and undiagnosed (by fasting glucose [FG] only), as well as impaired FG have an increased risk of coronary heart disease (CHD), compared with those with normal FG. Elevations in FG levels, even in normoglycemic subjects (<110 mg/dl), may be significantly related to CHD morbidity and mortality. Improving lipid profiles and blood pressure can decrease both CHD morbidity and mortality in these patients. We evaluated the relation of glucose status to lipid levels, other risk factors, and prevalence of CHD using the 1997 American Diabetes Association diagnostic criteria in a representative sample of United States adults studied in the Third National Health and Nutrition Examination Survey from 1988 to 1994. Impaired FG, diagnosed DM, and undiagnosed DM were more prevalent in older age groups; those > or =65 years had increased prevalence compared with those <50 years old (rate ratios for IFG, DM-FG, and history of DM were 3.5, 4.8, and 10.8, respectively). Glycosylated hemoglobin levels were increased by glucose status. The frequency of known CHD risk factors also increased with worsening glucose status. Age-adjusted CHD prevalence was increased with impaired FG (rate ratio 1.47), DM-FG (rate ratio 1.56), and history of DM (rate ratio 1.72), compared with normal FG. Adjusting for age and other CHD risk factors, hyperglycemia was no longer significantly associated with CHD prevalence. Lipid values, especially high-density lipoprotein cholesterol, hypertension, and other CHD risk factors were more strongly associated with CHD than glucose status. Thus, patients with impaired FG, DM-FG, and history of DM should be considered at higher risk for CHD morbidity and mortality. However, hyperglycemia, per se, does not explain the excess risk. In addition to glucose, lipid profiles and blood pressure should be periodically monitored and appropriate treatment provided to reduce morbidity and mortality from CHD.

Patients with type 2 diabetes mellitus have higher risk for acute pancreatitis compared with those without diabetes.

Aim: The aetiology of acute pancreatitis (AP) is complex, and many risk factors for AP are shared by patients with type 2 diabetes mellitus (T2DM). However, few have assessed risk factors for AP specifically in T2DM patients.

Initial monotherapy with either metformin or sulphonylureas often fails to achieve or maintain current glycaemic goals in patients with Type 2 diabetes in UK primary care

Aims  To describe initial achievement of glycaemic targets and subsequent hyperglycaemia in patients with Type 2 diabetes managed with oral agent monotherapy in UK primary care from 1998 to 2004.

Glycaemic control among patients with type 2 diabetes mellitus in seven European countries: findings from the Real‐Life Effectiveness and Care Patterns of Diabetes Management (RECAP‐DM) study

Objective:  This study was undertaken to assess glycaemic control as well as changes in glycaemic control over time in patients with type 2 diabetes mellitus (T2DM) who added a sulphonylurea (SU) or thiazolidinedione (TZD) to their metformin monotherapy in typical treatment settings within seven European countries.

The influence of age and body mass index on the metabolic syndrome and its components.

Objective:  The aim of this study was to evaluate the influence of ageing and body mass index (BMI) on the revised National Cholesterol Education Program (NCEP)‐defined metabolic syndrome, its components, diabetes and coronary heart disease prevalence using the Third National Health and Nutrition Examination Survey.

Economic and clinical impact of inpatient diabetic hypoglycemia.

OBJECTIVE To assess the clinical and economic impact of hypoglycemia that develops during hospitalization of patients with diabetes. METHODS In this retrospective cohort study, data from 70 hospitals were used to identify the first inpatient encounter for adult patients with diabetes. Patients were included if all blood glucose measurements were 70 mg/dL or higher during the first 24 hours and their primary discharge diagnosis was for a condition other than hypoglycemia. Those who developed laboratory evidence of hypoglycemia (blood glucose <70 mg/dL after 24 hours) were compared with patients whose blood glucose values were all 70 mg/dL or higher. An alternative definition of hypoglycemia (blood glucose <50 mg/dL after 24 hours) was also evaluated. We adjusted for potential confounders with multivariate models. RESULTS Hypoglycemia had an adverse effect on all outcomes among more than 100,000 diabetic patients. After adjustment, patients with diabetes who developed hypoglycemia had higher charges (38.9%), longer lengths of stay (3.0 days), higher mortality (odds ratio, 1.07; 95% confidence interval, 1.02-1.11), and higher odds of being discharged to a skilled nursing facility (odds ratio, 1.58; 95% confidence interval, 1.48-1.69) than diabetic patients without hypoglycemia (P<.01 for all). In all cases, using the lower threshold (<50 mg/dL) to define hypoglycemia resulted in similar findings with a larger magnitude of differences. CONCLUSIONS Although a direct causal relationship cannot be inferred, these study findings suggest the importance of carefully maintaining euglycemia during hospitalizations. Whether the observed worse outcomes were due to hypoglycemia itself or whether they were a marker of worse outcomes due to other causes requires further research.

Patient-reported outcomes in a survey of patients treated with oral antihyperglycaemic medications: associations with hypoglycaemia and weight gain

Aim: To examine the association between medication side‐effects (SEs) and patient‐reported outcomes (PROs) among patients with type 2 diabetes treated with oral antihyperglycaemic agents (OAHAs).

Fear of hypoglycaemia: defining a minimum clinically important difference in patients with type 2 diabetes.

BackgroundTo explore the concept of the Minimum Clinically Important Difference (MID) of the Worry Scale of the Hypoglycaemia Fear Survey (HFS-II) and to quantify the clinical importance of different types of patient-reported hypoglycaemia.MethodsAn observational study was conducted in Germany with 392 patients with type 2 diabetes mellitus treated with combinations of oral anti-hyperglycaemic agents. Patients completed the HFS-II, the Treatment Satisfaction Questionnaire for Medication (TSQM), and reported on severity of hypoglycaemia. Distribution- and anchor-based methods were used to determine MID. In turn, MID was used to determine if hypoglycaemia with or without need for assistance was clinically meaningful compared to having had no hypoglycaemia.Results112 patients (28.6%) reported hypoglycaemic episodes, with 15 patients (3.8%) reporting episodes that required assistance from others. Distribution- and anchor-based methods resulted in MID between 2.0 and 5.8 and 3.6 and 3.9 for the HFS-II, respectively. Patients who reported hypoglycaemia with (21.6) and without (12.1) need for assistance scored higher on the HFS-II (range 0 to 72) than patients who did not report hypoglycaemia (6.0).ConclusionWe provide MID for HFS-II. Our findings indicate that the differences between having reported no hypoglycaemia, hypoglycaemia without need for assistance, and hypoglycaemia with need for assistance appear to be clinically important in patients with type 2 diabetes mellitus treated with oral anti-hyperglycaemic agents.

Validity of the Adherence Estimator in the Prediction of 9-Month Persistence With Medications Prescribed for Chronic Diseases: A Prospective Analysis of Data From Pharmacy Claims

OBJECTIVE The aim of this article was to assess the predictive validity of the Adherence Estimator--a 3-item instrument designed to estimate a patients propensity to adhere to medications prescribed for chronic disease. METHODS The Adherence Estimator was a 3-item part of a larger survey mailed to adults aged >or=40 years who had a qualifying index prescription filled in June 2008. A qualifying prescription was defined as one for a medication indicated for the treatment of 1 of 5 chronic diseases (cardiovascular disease, dyslipidemia [lipid-lowering drugs], diabetes [oral antihyperglycemics], osteoporosis [oral bisphosphonates], or asthma). Outcomes were compared between the adherence risk groups derived from the Adherence Estimator (low risk = score of 0, medium risk = score of 2-7, and high risk = score of 8-36). Treatment persistence over a period of 9 months was measured using pharmacy claims data. The primary outcome was the median proportion of days covered (PDC) by >or=1 medication during the first 9 months after the index fill. Secondary outcomes included adherence to the index medication, defined as PDC dichotomized to >or=0.80 or <0.80; rate of obtaining a second fill within 30 days of the index fill; and medication possession ratio (MPR) for refill adherence. RESULTS There were 1676 usable responses. Ages ranged from 40 to 88 years, with a mean of 64.6 years. Almost two thirds (1076/1676 [64.2%]) of the sample were female, and 1483/1676 (88.5%) were white. Statistically significant associations for all 3 pairwise comparisons (low vs medium risk, low vs high risk, and medium vs high risk) were observed between the Adherence Estimator risk groups for: (1) median PDC (0.655, 0.598, and 0.484 in the low-, medium-, and high-risk groups, respectively [all, false discovery rate [FDR] <0.05]); (2) PDC categorized (293/711 [41.21%], 200/588 [34.01%], and 105/377 [27.85%] [all, FDR <0.05]); and (3) rate of obtaining a second fill for the index medication within 30 days (489/711 [68.78%], 374/588 [63.61%], and 207/377 [54.91%] [all, FDR <0.05]). The low- and high-risk groups differed from one another on: (1) persistence with the index medication at 9 months (265/711 [37.27%] and 95/377 [25.20%]); (2) persistence with >1 medication at 9 months (291/711 [40.93%] and 108/377 [28.65%]); and (3) obtaining a second fill for any medication within 30 days (501/711 [70.46%] and 219/377 [59.09%]) (all, P < 0.05). The low- and high-risk groups differed significantly from one another in MPR for refill adherence (0.912 vs 0.866). Results observed within diseases mirrored those for the total sample, but with less precision. CONCLUSION In the present analysis of the validity of the Adherence Estimator in predicting adherence, baseline propensity to adhere to medications prescribed for chronic diseases was statistically associated with several measures of adherence and persistence, as derived from pharmacy claims data, over a 9-month period.

Risk of acute renal failure in patients with Type 2 diabetes mellitus

Diabet. Med. 29, 614–621 (2012)