Fred W Whitehouse

Bone Loss and Bone Turnover in Diabetes

There have been conflicting reports about the effect of diabetes on bone density. In 1978, we studied 109 patients, 46 with type I and 63 with type II diabetes; ∼12 years later we restudied 35 of the 66 surviving patients. In the original study, radial bone density did not differ significantly between patients with either type of diabetes but was significantly lower than in nondiabetic control subjects. In eight osteopenic patients, bone formation rate and other histological indexes of osteoblast recruitment and function were markedly depressed compared with those in nondiabetic control subjects. In patients remeasured ∼2.5 years (41 patients) and ∼12.5 years (35 patients) after baseline, bone loss had continued at the expected rate in patients with type I diabetes, with maintenance of the same deficit, but was slower than expected in patients with type II diabetes, such that the initial deficit had been completely corrected. In six of the eight patients who had undergone bone biopsy, one with type I and five with type II diabetes, the mean bone mineral density z-score of the spine and femoral neck ∼12 years later was >0 and in one subject was significantly higher than normal at both sites. Based on these data and on previous studies, we propose that in patients with diabetes, low bone formation retards bone accumulation during growth, metabolic effects of poor glycemic control lead to increased bone resorption and bone loss in young adults, and low bone turnover retards agerelated bone loss. These effects account for low bone density in young patients with type I diabetes and normal or increased bone density in older patients with type II diabetes.

A Web-Based Diabetes Care Management Support System

BACKGROUND Because of the often asymptomatic nature of diabetes and the long period between sustained hyperglycemia and observable complications, appropriate diabetes care relies on a long-term program of secondary prevention. Yet routine monitoring and screening among patients with diabetes is less than optimal. To support the provision of routine care to patients with diabetes, the Center for Health Services Research, Henry Ford Health System (Detroit), developed a Web-based Diabetes Care Management Support System (DCMSS). A nonrandomized, longitudinal study was conducted (January 1, 1998-October 31, 1999) with 13,325 health maintenance organization patients with diabetes who were aligned to 190 primary care providers practicing in 31 primary care clinics. RESULTS Three DCMSS features--clinical practice guidelines, patient registries, and performance reports--were made available via a corporate intranet within an existing electronic medical record. The effect of DCMSS usage frequency was evaluated on the likelihood of a patients receipt of glycated hemoglobin testing, lipid profile testing, and retinal examinations. Logistic regression models controlling for patient sociodemographic and clinical characteristics, and the testing history of the patient, the primary care physician, and the primary care clinic, were fit using generalized estimating equation methods. The more often a physician used DCMSS, the more likely his or her patients were to receive lipid profile testing (OR [odds ratio] = 1.01, 95% CI [confidence interval] = 1.01-1.02). Compared with patients of physicians who never used the system, patients of physicians who initiated 12 sessions were an estimated 19% more likely (95% CI = 7%-33%) to receive lipid profile testing. The analyses also suggested that the likelihood of a patient receiving a retinal exam was associated with system usage (OR = 1.01, 95% CI = 1.01-1.01). No relationship was found between system use and glycated hemoglobin testing. CONCLUSIONS Computerized systems of clinical practice guidelines, patient registries, and performance feedback may help improve the rate of routine testing among patients with diabetes.

Impact of glycemic control strategies on the progression of diabetic peripheral neuropathy in the Bypass Angioplasty Revascularization Investigation 2 Diabetes (BARI 2D) Cohort.

OBJECTIVE The Bypass Angioplasty Revascularization Investigation 2 Diabetes (BARI 2D) trial demonstrated similar long-term clinical effectiveness of insulin-sensitizing (IS) versus insulin-providing (IP) treatments for type 2 diabetes on cardiovascular outcomes in a cohort with documented coronary artery disease. We evaluated the effects of randomized glycemic control strategy (IS vs. IP) on the prevalence and incidence of diabetic peripheral neuropathy (DPN). RESEARCH DESIGN AND METHODS DPN (defined as Michigan Neuropathy Screening Instrument [MNSI] clinical examination score >2) was assessed at baseline and yearly for 4 years. DPN prevalence and incidence were compared by intention-to-treat modeling by logistic generalized estimating equation models for prevalence and Kaplan-Meier estimates and Cox regression models for incidence rates. RESULTS Results are reported for 2,159 BARI 2D participants (70% males) with valid baseline and at least one follow-up MNSI score (mean age 62 ± 9 years, mean HbA1c 7.7 ± 1.6%, diabetes duration 10 ± 9 years). There were no differences in the prevalence of DPN between the IS and the IP groups throughout the 4 years of follow-up. In 1,075 BARI 2D participants with no DPN at baseline, the 4-year cumulative incidence rate of DPN was significantly lower in the IS (66%) than in the IP (72%) strategy group (P = 0.02), which remained significant after adjusting for the in-trial HbA1c (P = 0.04). In subgroup analyses, IS strategy had a greater benefit in men (hazard ratio 0.75 [99% CI 0.58–0.99], P < 0.01). CONCLUSIONS Among patients with type 2 diabetes followed for up to 4 years during BARI 2D, a glycemic control therapy with IS significantly reduced the incidence of DPN compared with IP therapy and may add further benefit for men.

Teaching the Person with Diabetes: Experience with a Follow-up Session

We studied 371 diabetic patients who attended an outpatient follow-up session after completing an in-patient diabetes education program. Identified gaps in information on diabetes care included problems with understanding the prescribed diet (155 patients), incorrect urine testing (30 patients), and unacceptable technics of insulin administration (26 patients). We also reviewed 178 consecutive patients who had been invited to this follow-up session to ascertain how often readmission to the hospital occurred. 88 of these patients attended a follow-up session while 90 patients did not attend. Over the ensuing 5 yr, the latter group had a significantly higher readmission rate (P < 0.01), yet readmissions for education-related reasons (ketoacidosis, foot infections, and hypoglycemia) were not significantly different. Even when diabetic patients have recently attended education sessions on living with diabetes, attendance at regular follow-up sessions is encouraged to reinforce learning and to identify persisting gaps in information.

Motor Vehicles, Hypoglycemia, and Diabetic Drivers

Individuals with diabetes are increasingly persuing employment in fields previously restricted as a result of the development of chronic complications. Improved glycemic control resulting from use of sophisticated insulin delivery and monitoring systems has also led to the recognition of recurrent hypoglycemia as a potential major clinical and occupational hazard. No data concerning the occupational safety of individuals with insulin-treated diabetes mellitus (ITDM) are available. We review the literature on diabetic drivers in an effort to examine the impact of certification of ITDMs as commercial drivers. In the absence of significant worldwide experience with ITDMs as commercial drivers, the discussion is necessarily based on projected accident rates derived from data on frequency of hypoglycemia. These studies are universally flawed by variable definitions of hypoglycemia, ascertainment bias, and patient selection. They do, however, provide a worst-case/best-case scenario for discussion. It is imperative that any expansion of employment opportunities for ITDMs be followed carefully with prospective studies to assess the impact on public safety.

Comparison of a novel insulin bolus-patch with pen/syringe injection to deliver mealtime insulin for efficacy, preference, and quality of life in adults with diabetes: a randomized, crossover, multicenter study.

OBJECTIVE This study compared the efficacy, safety, device satisfaction, and quality of life (QOL) in people with diabetes using an insulin bolus-patch versus current devices (pen/syringe) to deliver mealtime insulin. RESEARCH DESIGN AND METHODS Thirty-eight subjects with diabetes (26 with type 1 and 12 with type 2) were randomized to bolus-patch or current injection device (55% pen and 45% syringe) to deliver mealtime insulin in a multicenter, 6-week crossover study. Efficacy was assessed by equivalence in mean daily seven-point blood glucose (MDBG). Safety assessments included severe hypoglycemia episodes, adverse device effects (ADEs), and adverse events (AEs). Device satisfaction was determined by the validated Insulin Delivery System Rating Questionnaire (IDSRQ) and QOL by the validated Diabetes Specific QOL Scale (DSQOLS). RESULTS Using bolus-patch, MDBG (mean±SE) was equivalent to that using pen/syringe (8.61±0.28 vs. 9.02±0.26 mmol/L; P=0.098). SD of the seven-point blood glucose measurements was lower using bolus-patch (3.18±0.18 vs. 3.63±0.17 mmol/L; P=0.004), as was the coefficient of variation (CV) (37.2±1.7 vs. 40.3±1.7%; P=0.046). Hemoglobin A1c, 1,5-anhydroglucitol, fructosamine, and insulin use were similar between groups. There were no severe hypoglycemia episodes or serious ADEs. Between-device AEs were comparable. Subjects scored better on six of seven subscales on the DSQOLS and five of six subscales on the IDSRQ while using bolus-patch versus pen/syringe. At study completion, 76% of subjects would choose to switch to bolus-patch (P=0.001). CONCLUSIONS Delivery of mealtime insulin with bolus-patch compared with pen/syringe resulted in equivalent MDBG, lower SD and CV of seven-point blood glucose measurements, good safety, significant device satisfaction, and improved QOL.

Saving a Foot and Salvaging a Limb

Nothing aggrieves a person like the amputation of a body part. The diabetic person faces this grim possibility more often than do his peers without diabetes. The report by the National Commission on Diabetes states that people with diabetes face five times more leg and foot amputations. At the Henry Ford Hospital, half of the nontraumatic amputations of the leg are done in diabetic persons, even though only 10% of hospitalized patients have diabetes. These amputees are mostly older patients with non-insulin-dependent diabetes. Yet, the threat of foot amputations also looms large to those patients with insulin-dependent diabetes, especially when their disease exceeds 20 yr. Block and I studied 125 consecutive diabetic patients who underwent a below-knee amputation: their ages averaged 67 yr, with a range of from 36 to 85 yr.

Determinants of successful glycemic control among participants in the BARI 2D Trial: A Post-hoc Analysis

OBJECTIVE The BARI 2D trial compared insulin provision (IP) versus insulin sensitization (IS) for the primary outcome of total mortality in participants with T2DM and cardiovascular disease (CVD). In this analysis we examine baseline characteristics that are associated with successful long-term glycemic control. RESEARCH DESIGN AND METHODS In a 2×2 factorial design, 2368 participants were randomized to either IP or IS therapy, and to either prompt revascularization with medical therapy or medical therapy alone. Successful long-term glycemic control (success) was defined by simultaneously meeting 1) a mean HbA1c level of <7.0% after each participants third year of follow-up period, and 2) adherence with medications only from the assigned glycemic treatment arm during >80% of the BARI 2D follow-up. The association between baseline variables and success was determined using unadjusted and adjusted logistic regression models. RESULTS 1917 participants (962 IP and 955 IS participants) had sufficiently long follow-up and data for this analysis. Among these IP and IS participants, 235 and 335 participants met both criteria of success, respectively (p<0.001). Those not on insulin at entry had higher odds of success (OR 2.25; CI 1.79-2.82) when treated with IS versus IP medications, irrespective of baseline HbA1c levels. Younger age, shorter duration of T2DM, and lower HbA1c at baseline were also each independently associated with higher success when treated with IS versus IP medications. CONCLUSION Patients similar to those in the BARI 2D trial may have a higher chance of achieving success with IS versus IP medications if they are younger, have shorter duration of T2DM, have lower HbA1c levels, have moderate or strenuous physically activity, and are not on insulin. In contrast, increasing age, longer duration of T2DM, higher HbA1c, and insulin therapy are associated with increased chance of success if treated with IP medications.