Hugh D. Tildesley

Barriers to effective insulin treatment: the persistence of poor glycemic control in type 2 diabetes

Abstract Background: Contrary to longstanding recommendations on type 2 diabetes (T2D) management, the de facto standard of care in Canada includes lag times of many years prior to introducing effective glycemic control. Even patients transitioned to insulin may continue to experience poor glycemic control, with attendant diabetic complications, suggesting poor adherence or inadequate dose titration. Objective: To identify barriers to timely and effective use of insulin in T2D. Methods: PubMed searches were conducted to find research articles on insulin initiation, adherence and intensification. Also, because recent data on the consequences of intensive glycemic control may be taken as justification for relaxing glycemic targets, a secondary search on this literature was conducted, including the UKPDS and ACCORD trials, plus post hoc and meta-analyses of these data. No formal evaluation of level of evidence was conducted while researching this narrative literature review. Findings: Timely, effective glycemic control remains an important clinical goal but is complicated by patient, physician and treatment factors. Patient barriers to accepting insulin initiation include fear of hypoglycemia, injections and weight gain, and reluctance to accommodate the inflexible timing of scheduled insulin doses. Adherence issues, including dose omission, are common and are associated with some of the same factors. Fear of hypoglycemia also underlies many physicians’ reluctance to prescribe insulin. Caregivers’ failure to provide training or answer questions about insulin’s risks and benefits was also associated with low patient adherence. Poor communication may also be at fault when patients on insulin fail to titrate or intensify their treatment adequately. Conversely, glycemic control can be significantly improved by facilitating ongoing communication between patients and caregivers. Discussion: Although innovations in injectable therapy for T2D may help address the current pattern of poor glycemic control, improved communication between patients and caregivers is also a powerful approach and can be implemented with existing therapies.

Metformin's contraindications should be contraindicated

Metformin has been used for over 40 years for patients with type 2 diabetes mellitus.[1][1] With over 40 million patient-years of use as of 1999,[1][1] there is now evidence that the drug decreases the risk of morbidity and death when used to treat type 2 diabetes.[2][2] However, concern remains

NIDDM in the elderly

OBJECTIVE We conducted this study to assess the metabolic alterations in elderly patients with NIDDM. RESEARCH DESIGN AND METHODS Healthy, lean (n = 15; age, 73 ± 1 years; BMI, 23.8 ± 0.5 kg/m2), and obese (n = 10; age, 71 ± 1 years; BMI, 28.9 ± 1.2 kg/m2) control subjects and lean (n = 10; age, 75 ± 2 years; BMI, 24.0 ± 0.5 kg/m2) and obese (n = 23; age, 73 ± 1 years; BMI, 29.9 ± 0.7 kg/m2) NIDDM patients underwent a 3-h glucose tolerance test, a 2-h hyperglycemic glucose clamp study, and a 3-h euglycemic glucose clamp study with tritiated glucose methodology to measure glucose production and disposal rates. RESULTS Waist-to-hip ratio (WHR) was greater in both lean and obese NIDDM patients than in control subjects. Insulin responses during the oral glucose tolerance test were similar in obese subjects (control subjects: 417 ± 64 pmol/l; NIDDM patients: 392 ± 47 pmol/l) but were reduced in lean NIDDM patients (control subjects: 374 ± 34 pmol/l; NIDDM patients: 217 ± 20 pmol/l, P < 0.01). Lean and obese NIDDM patients had absent first-phase insulin responses during the hyperglycemic clamp. Second-phase insulin responses were reduced in lean (P < 0.01 vs. control subjects by analysis of variance) but not obese NIDDM patients. Hepatic glucose output was not increased in lean or obese NIDDM patients. Steady-state (150–180 min) glucose disposal rates were 16% less in lean NIDDM patients (control subjects: 8.93 ± 0.37 mg.kg LBM (lean body mass)−1 · min−1; NIDDM patients: 7.50 ± 0.28 mg · kg LBM−1 · min−1, P < 0.05) and 37% less in obese NIDDM patients (control subjects: 8.17 ± 0.38 mg · kg LBM−1 · min−1; NIDDM patients: 5.03 ± 0.36 mg · kg LBM−1 · min−1, P < 0.001). CONCLUSIONS Lean elderly NIDDM patients have a profound impairment in glucose-induced insulin release but mild resistance to insulin-mediated glucose disposal. Obese elderly NIDDM patients have adequate circulating insulin, but marked resistance to insulin-mediated glucose disposal. Hepatic glucose output is not increased in elderly NIDDM patients.

Effect of Internet Therapeutic Intervention on A1C Levels in Patients With Type 2 Diabetes Treated With Insulin

OBJECTIVE To assess the effect of an Internet-based glucose monitoring system (IBGMS) on A1C levels in patients with type 2 diabetes treated with insulin. RESEARCH DESIGN AND METHODS This trial involved 50 patients randomly assigned to receive either conventional treatment alone or with additional follow-up through an IBGMS for 6 months. Patients randomized to the intervention group uploaded blood glucose readings every 2 weeks to a secure Web site for review and receipt of feedback from their endocrinologist. A1C and laboratory test results were collected at 0, 3, and 6 months. RESULTS The baseline parameters were not significantly different. Over a 6-month follow-up, A1C dropped from 8.8 to 7.6% (P < 0.001) in the intervention group compared with 8.5 to 8.4% (P = 0.51) in the control group. CONCLUSIONS The use of IBGMS significantly improved A1C levels in patients with type 2 diabetes treated with insulin.

Gestational Diabetes Mellitus Outcome in 394 Patients

OBJECTIVE To determine whether women with gestational diabetes mellitus (GDM) and their offspring have pregnancy outcomes and complications of pregnancy that are different from those in the general obstetric population. METHODS Through medical record coding, we identified women with GDM and a singleton pregnancy with cephalic presentation who delivered at St. Pauls Hospital between January 1, 1995, and December 31, 2001. In total, 394 births were analyzed and their outcomes compared with those of a control group of 100 non-diabetic women with the same gestational age (38 weeks) at delivery. RESULTS Women with gestational diabetes were of lesser parity (P 0.05), appreciably older (P 0.05), and less likely to be Caucasian (P 0.005) than the general obstetric population. Women with GDM also had a higher risk of Caesarean section (P 0.05), gestational hypertension (P 0.05), and large for gestational age (LGA) deliveries (P 0.005). Of women with GDM, those treated with insulin had a higher incidence of LGA deliveries than those on diet therapy alone. The incidence of respiratory distress syndrome and of need for phototherapy was similar in babies whose mothers had GDM and in those whose mothers did not. CONCLUSION Although the rate of complications remains low, GDM creates a predisposition to increased maternal and neonatal complications.

Efficacy of A1C Reduction Using Internet Intervention in Patients with Type 2 Diabetes Treated with Insulin

ABSTRACT OBJECTIVE: To assess the effect of an Internet-based glucose monitoring system (IBGMS) on glycated hemoglobin (A1C) levels in patients with type 2 diabetes mellitus treated with insulin. METHODS: Fifty patients were randomly assigned to receive conventional care alone (control) or additional follow-up via IBGMS for 6 months. Patients randomized to the IBGMS group uploaded blood glucose readings to a secure website every 2 weeks to receive feedback from their endocrinolo- gist. After 6 months, all patients returned to conventional care. A1C and laboratory test results were collected at 0, 3, 6 and 12 months. RESULTS: Baseline parameters were not significantly different. After a 6-month follow-up, A1C dropped from 8.8% to 7.6% (p CONCLUSION: IBGMS significantly improved A1C levels in patients with type 2 diabetes treated with insulin, but this effect was lost with cessation of the intervention.

Miglitol, an α-glucosidase inhibitor, prevents the metformin-induced fall in serum folate and vitamin B12 in subjects with type 2 diabetes

Abstract Since folate and vitamin B 12 absorption may be increased by colonic bacterial activity, their status may be improved by miglitol, an α-glucosidase inhibitor of potential use in the treatment of diabetes. To test this, subjects with type 2 diabetes were treated for 9 months in a double-blind, randomized controlled fashion with either placebo (n=45), miglitol (n=45), metformin (n=62), or a combination of miglitol and metformin (n=47). Glycated hemoglobin (HbA 1c ), serum and red cell folate and serum vitamin B 12 were measured and 3-day dietary records obtained before and after therapy. Compared to placebo, all 3 active treatments significantly reduced HbA 1c , metformin to a greater extent than miglitol and the combination to a greater extent than metformin. Dietary folate intake did not change on any treatment. Serum folate and vitamin B 12 , respectively, did not change on placebo, but fell by 14% and 15% on metformin and rose by 12% and 23% on miglitol. The changes in folate and vitamin B 12 concentrations on metformin were significantly different from those on miglitol. On combination therapy, both folate and vitamin B 12 tended to rise, but the difference from metformin was only significant for folate. These data support the hypothesis that increased carbohydrate delivery to the colon increases intestinal biosynthesis of folate. The combination of miglitol with metformin may prevent the metformin-induced fall in serum folate and vitamin B 12 .

Counterregulatory Hormone Responses After Long-Term Continuous Subcutaneous Insulin Infusion With Lispro Insulin

OBJECTIVE To determine whether the long-term use of insulin lispro (LP) affects the counterregulatory hormone response to hypoglycemia. RESEARCH DESIGN AND METHODS Ten patients (age range 26-51 years; ratio of men to women 9:1; BMI 24.9 ± 0.48; mean HbA1c 7.84 ± 0.25%) with IDDM, treated with continuous subcutaneous insulin infusion (CSII; Disetronic H-TRON V100) were studied using a double-blind, crossover design. Patients were randomized to LP or human regular insulin (HR) for 3 months and then crossed over to the other insulin for an additional 3 months. All meal boluses were given 0-5 min before breakfast, lunch, and dinner. Counterregulatory hormone responses to a stepped hypoglycemic clamp (consecutive glucose levels in mmol/l: 4.2; 3.5; 2.8, each for 1 h) were evaluated at the end of each treatment period. RESULTS HbA1c was significantly lower with LP versus HR (7.47 ± 0.28% vs. 7.9 ± 0.26%, P = 0.04). The incidence of hypoglycemia per 30 days (capillary blood glucose < 3.0 mmol/l and/or symptoms) during the last month of the study was significantly lower with LP versus HR (8.7 ± 2.9 vs. 11.8 ± 2.9, P = 0.03). The total daily insulin dosage was not different in the two treatment periods. There was no episode of severe hypoglycemia or diabetic ketoacidosis. The peak growth hormone, cortisol, glucagon, and epinephrine responses during the same period of hypoglycemia were not different for each treatment period. CONCLUSIONS The use of LP in CSII results in improved glycemic control and a decrease in the frequency of hypoglycemia without adversely affecting counterregulatory hormone response to hypoglycemia.

Patient preferences for diabetic retinopathy health States.

PURPOSE. To develop standardized descriptions of health states that characterize vision-specific functional impacts of diabetic retinopathy (DR) according to levels of visual acuity and contrast sensitivity and to elicit preferences for these health states from persons with DR and assign weighted values to them. METHODS. Vision-specific descriptions of health states were developed based on a literature review and patient and physician interviews. The content was based on items from the National Eye Institute Visual Functioning Questionnaire (VFQ) and reflected functional impacts experienced by DR patients. Values were assigned to the range of health states, anchored by the extremes full vision and death, by using the time-tradeoff method in a sample of 98 Canadian DR patients from three clinical centers. RESULTS. The mean age of the sample was 60.4 years, and 56% were men. Mean preferences decreased from 0.98 (better-eye logMAR [Snellen equivalent] acuity, > or =20/40; worse-eye Snellen equivalent, > or =20/200) to 0.67 (Snellen equivalent visual acuity, < or =20/200, contrast sensitivity, < or =21 letters bilaterally). Preferences decreased with increasing severity of functional deficits and did not vary significantly by sex, age, VFQ quartile, or better- or worse-eye acuity. CONCLUSIONS. This is the first study that has been conducted to estimate preferences for standardized DR-specific health states, accounting for visual acuity and contrast sensitivity in both eyes. The results showed that the development and progression of DR are associated with substantial declines in preferences. In addition to the progressively greater impact from declining ETDRS visual acuity and contrast sensitivity, preference weights declined with increasing bilateral disparity. These preference values are useful for comparing the cost effectiveness of ophthalmic treatments.

Sex Disparities in Effects of Cystic Fibrosis-Related Diabetes on Clinical Outcomes: A Matched Study

BACKGROUND Cystic fibrosis-related diabetes (CFRD) is an increasingly prevalent comorbidity factor for patients with cystic fibrosis (CF). CFRD has been associated with an accelerated decline in clinical parameters and an increased mortality rate. OBJECTIVES To investigate the clinical impact of CFRD on pulmonary function and clinical status using a matched study design to further explore potential causality. METHODS Charts from the adult CF clinic at St Pauls Hospital (Vancouver, British Columbia) were retrospectively reviewed. Forty CFRD patients with and without fasting hyperglycemia were matched to CF patients with nondiabetic glucose tolerance based on sex, age and forced expiratory volume in 1 s (FEV(1)). RESULTS Sixteen of 40 CFRD patients (40%) died compared with nine of 40 patient controls (23%) (P=0.13). CFRD patients were more likely to experience declines in FEV(1) (P<0.01), especially women (P<0.01). Patients with CFRD were not more likely to be hospitalized (P=0.39). Body mass index did not differ between groups. CONCLUSIONS Patients with CFRD had higher rates of FEV(1) deterioration than nondiabetic patients with CF, and showed a trend toward increased mortality. The present study suggests that CFRD has a significant clinical impact and should be carefully considered when evaluating the status of CF patients.