Mark R. Burge

Hypoglycaemia in Elderly Patients with Diabetes Mellitus

Achieving target glycaemic goals while avoiding hypoglycaemia is a major challenge in the management of elderly patients with diabetes mellitus. Repeated episodes of hypoglycaemia may cause extreme emotional distress in such patients, even when the episodes are relatively mild. Moreover, evidence is mounting that hypoglycaemia among elderly patients is a very real and costly health concern. The strongest predictors of severe hypoglycaemia in the elderly are advanced age, recent hospitalisation and polypharmacy. Education is the key to preventing recurrent or severe hypoglycaemia. As such, there should be close coordination of care between the patient, physician and all other healthcare providers in identifying the cause of hypoglycaemia in elderly patients, and appropriate steps should be taken to prevent further episodes. Prevention of hypoglycaemia has the potential to improve psychosocial aspects of elderly health, including enhanced quality of life, boosted confidence, improved compliance with antidiabetic regimens and avoidance of long-term complications.Since the elderly population represents a unique group, it is imperative to focus on the aetiologies that are exclusive to this group. Advanced age itself is a risk factor for hypoglycaemia, and elderly patients with comorbidities are at increased risk when they are hospitalised. Elderly patients with diabetes often have compromised renal function, which intereferes with drug elimination and thus predisposes them to prolonged life-threatening hypoglycaemia. In addition, patients on five or more prescription medications are prone to drug-associated hypoglycaemia. Although sulfonylurea-associated hypoglycaemia is common, drugs such as ACE inhibitors and nonselective β-adrenoceptor antagonists can also predispose patients to hypoglycaemia. Greater attention should be paid to the avoidance of hypgolycaemia in nursing home residents. Recurrent hypoglycaemia in elderly patients is not only detrimental to achieving good glycaemic control, it is also a substantial economic burden.Once the causes of hypoglycaemia have been identified, it is crucial to formulate and institute a prevention plan. Firstly, global evaluation of the patient should be carried out to identify possible predisposing risk factors. Secondly, target glycaemic goals should be tailored to each patient. Thirdly, selection of antidiabetic agents should be judicious, then patients and family should be educated to recognise and treat hypoglycaemia. Finally, coordinated care should be provided to identify, treat and prevent hypoglycaemia.

Thiazolidinediones: A Comparative Review of Approved Uses

Thiazolidinediones are a powerful and clinically important new class of oral antidiabetic agents that act by improving insulin sensitivity. Troglitazone is the prototype drug in this class but was withdrawn from the market in March 2000 due to its association with idiosyncratic hepatotoxicity. Currently two thiazolidinediones, rosiglitazone and pioglitazone, are U.S. Food and Drug Administration (FDA) approved for treatment of type 2 diabetes. These agents bind to and activate peroxisome proliferator-activator receptor gamma (PPAR-gamma) and work by altering the expression of genes involved in glucose uptake, glucose disposal, and lipid metabolism. The drugs differ in receptor binding and potency due to differences in their side chain moieties. These agents are rapidly absorbed from the gastrointestinal tract and are metabolized mainly in the liver. Rosiglitazone is FDA approved for monotherapy and for use in combination therapy with metformin or sulfonylureas. Pioglitazone is FDA approved for monotherapy as well as for use in combination therapy with metformin, insulin, or sulfonylureas. These drugs may also cause significant changes in plasma lipid concentrations, and improved insulin sensitivity may improve ovulatory function and fertility in women with polycystic ovary syndrome. The most serious side effect of the thiazolidinediones is hepatotoxicity. Although rosiglitazone and pioglitazone were not associated with hepatotoxicity in premarketing clinical trials, there were two recent case reports of idiosyncratic hepatotoxicity in patients treated with rosiglitazone. In addition, these agents may be associated with edema and some hematological changes. The purpose of this review is to provide an overview of the two currently approved thiazolidinediones and to suggest an approach for their safe and rational use.

Mind-Body Practices for Posttraumatic Stress Disorder

Background Mind-body practices are increasingly used to provide stress reduction for posttraumatic stress disorder (PTSD). Mind-body practice encompasses activities with the intent to use the mind to impact physical functioning and improve health. Methods This is a literature review using PubMed, PsycINFO, and Published International Literature on Traumatic Stress to identify the effects of mind-body intervention modalities, such as yoga, tai chi, qigong, mindfulness-based stress reduction, meditation, and deep breathing, as interventions for PTSD. Results The literature search identified 92 articles, only 16 of which were suitable for inclusion in this review. We reviewed only original, full text articles that met the inclusion criteria. Most of the studies have small sample size, but findings from the 16 publications reviewed here suggest that mind-body practices are associated with positive impacts on PTSD symptoms. Mind-body practices incorporate numerous therapeutic effects on stress responses, including reductions in anxiety, depression, and anger, and increases in pain tolerance, self-esteem, energy levels, ability to relax, and ability to cope with stressful situations. In general, mind-body practices were found to be a viable intervention to improve the constellation of PTSD symptoms such as intrusive memories, avoidance, and increased emotional arousal. Conclusions Mind-body practices are increasingly used in the treatment of PTSD and are associated with positive impacts on stress-induced illnesses such as depression and PTSD in most existing studies. Knowledge about the diverse modalities of mind-body practices may provide clinicians and patients with the opportunity to explore an individualized and effective treatment plan enhanced by mind-body interventions as part of ongoing self-care.

PTSD symptom reduction with mindfulness-based stretching and deep breathing exercise: randomized controlled clinical trial of efficacy.

CONTEXT Abnormal cortisol levels are a key pathophysiological indicator of post-traumatic stress disorder (PTSD). Endogenous normalization of cortisol concentration through exercise may be associated with PTSD symptom reduction. OBJECTIVE The aim of the study was to determine whether mindfulness-based stretching and deep breathing exercise (MBX) normalizes cortisol levels and reduces PTSD symptom severity among individuals with subclinical features of PTSD. DESIGN AND SETTING A randomized controlled trial was conducted at the University of New Mexico Health Sciences Center. PARTICIPANTS Twenty-nine nurses (28 female) aged 45-66 years participated in the study. INTERVENTION Sixty-minute MBX sessions were conducted semiweekly for 8 weeks. MAIN OUTCOME MEASURES Serum cortisol was measured, and the PTSD Checklist-Civilian version (PCL-C) was performed at baseline and weeks 4, 8, and 16. RESULTS Twenty-nine participants completed the study procedures, 22 (79%) with PTSD symptoms (MBX, n = 11; control, n = 11), and 7 (21%) without PTSD (BASE group). Eight-week outcomes for the MBX group were superior to those for the control group (mean difference for PCL-C scores, -13.6; 95% confidence interval [CI], -25.6, -1.6; P = .01; mean difference for serum cortisol, 5.8; 95% CI, 0.83, 10.8; P = .01). No significant differences were identified between groups in any other items. The changes in the MBX group were maintained at the 16-week follow-up (P = .85 for PCL-C; P = .21 for cortisol). Our data show that improved PTSD scores were associated with normalization of cortisol levels (P < .05). CONCLUSIONS The results suggest that MBX appears to reduce the prevalence of PTSD-like symptoms in individuals exhibiting subclinical features of PTSD.

Meal Composition is a Determinant of Lispro-Induced Hypoglycemia in IDDM

OBJECTIVE Lispro is a newly FDA-approved analog of human insulin that will be widely used in patients with IDDM. This insulin, however, may have an increased potential for hypoglycemia because of its very rapid subcutaneous absorption, especially in a setting of decreased carbohydrate intake. Using a short-term prospective randomized parallel group-study design, we studied the incidence of hypoglycemia when lispro was given before breakfast compared with regular human insulin. Since carbohydrate intake is a determinant of postprandial glycemia, we administered three isocaloric meals characterized by low, average, and high carbohydrate content. RESEARCH DESIGN AND METHODS Two groups of six IDDM subjects were randomized to receive 0.15 U/kg of lispro or regular human insulin subcutaneously before the ingestion of three 500-kcal breakfast meals of differing carbohydrate content on separate days. Lispro was administered at mealtime, and regular insulin was administered 30 min before mealtime. RESULTS Postprandial plasma glucose concentrations were decreased in the lispro group compared with the regular-insulin group for all three meal types (P < 0.05), and hypoglycemia developed more frequently and rapidly in the lispro group, compared with the regular-insulin group by survival analysis. Additionally, peak insulin concentrations were higher (P < 0.001) and peaked more rapidly (P < 0.05) in the lispro group, compared with the regular-insulin group. CONCLUSIONS We conclude that lispro has a tendency for early postprandial hypoglycemia compared with regular insulin in the setting of reduced carbohydrate intake. This fact should be told to patients who decide to switch from regular insulin to lispro. Health care professionals should instruct their IDDM patients to monitor glucose levels frequently after switching to lispro since adjustments in their carbohydrate intake and/or their lispro dosage may be necessary to avoid hypoglycemia.

Risks of Complication Following Thyroidectomy

AbstractOBJECTIVE: Because hypoparathyroidism is a serious complication of thyroidectomy, we attempted to elucidate factors determining the risk of this postoperative outcome. SETTING: Four tertiary care hospitals in Albuquerque, New Mexico. PATIENTS: A retrospective study of 142 patients who underwent total or subtotal thyroidectomy between 1988 and 1995. MEASUREMENTS AND MAIN RESULTS: Permanent hypoparathyroidism was defined as hypocalcemic symptoms plus a requirement for oral vitamin D or calcium 6 months after thyroidectomy. Factors analyzed to determine their contribution to the risk of persistent postoperative hypoparathyroidism were the indication for thyroidectomy, performance of a preoperative thyroid needle biopsy, type of surgery, postoperative pathology, presence and stage of thyroid carcinoma, resident surgeon involvement, and specialty of the surgeon performing the procedure. Surgical specialty and stage of thyroid carcinoma were independent risk factors for persistent postoperative hypoparathyroidism by multivariate analysis. Nine (29%) of 31 patients who had thyroidectomy by otolaryngologists met criteria for permanent hypoparathyroidism, and 6 (5%) of 111 patients who had thyroidectomy by general surgeons met the same criteria (p<.001). Adjustment for the effect of stage did not eliminate the effect of specialty (p=.006), and adjustment for the effect of specialty did not eliminate the effect of stage (p=.02), on the occurrence of postoperative hypoparathyroidism. CONCLUSIONS: We conclude from our data that patients undergoing thyroidectomy by an otolaryngologist may be at a higher risk of permanent postoperative hypoparathyroidism than patients who undergo thyroidectomy by a general surgeon. This may reflect differences in case selection or surgical approach or both.

Idiopathic hypogonadotropic hypogonadism in a male runner is reversed by clomiphene citrate

OBJECTIVE To assess the efficacy of estrogen antagonist therapy on the function of the hypothalamic-pituitary-testicular axis in a young male runner with significant morbidity attributable to idiopathic hypogonadotropic hypogonadism. DESIGN An uncontrolled case study. SETTING The outpatient endocrinology clinic of a university tertiary referral center. PATIENT(S) A 29-year-old male who has run 50 to 90 miles per week since 15 years of age and who presented with a pelvic stress fracture, markedly decreased bone mineral density, and symptomatic hypogonadotropic hypogonadism. INTERVENTION(S) Clomiphene citrate (CC) at doses up to 50 mg two times per day over a 5-month period. MAIN OUTCOME MEASURE(S) Serum concentrations of LH, FSH, and T before and after CC therapy, as well as clinical indicators of gonadal function. RESULT(S) Barely detectable levels of LH and FSH associated with hypogonadal levels of T were restored to the normal range with CC therapy. The patient experienced improved erectile function, increased testicular size and sexual hair growth, and an improved sense of well being. CONCLUSION(S) Exercise-induced hypogonadotropic hypogonadism exists as a clinical entity among male endurance athletes, and CC may provide a safe and effective treatment option for males with debilitating hypogonadism related to endurance exercise.

Diabetes Mellitus Associated with Atypical Anti-Psychotic Medications

Diabetes or hyperglycemia associated with the use of atypical anti-psychotic agents is a subject of growing concern among health care providers and the patients who use the drugs. Although much attention has been relegated to this topic in the mental health literature, there has been little attention devoted to it in the diabetes literature. The purpose of this report is to review the problem of diabetes mellitus associated with atypical anti-psychotic use from an endocrinology perspective. This paper will specifically present (a) a review of the increased prevalence of diabetes in the setting of schizophrenia, (b) a compilation and critical assessment of the existing publications that have documented the association of hyperglycemia and atypical anti-psychotic use, (c) a discussion of the potential mechanisms through which antipsychotics may lead to disturbances in glucose homeostasis, and (d) recommendations for the effective monitoring and treatment of affected patients.

Increased CD36 Expression Signals Monocyte Activation Among Patients With Type 2 Diabetes

OBJECTIVE To explore the hypothesis that CD36, a scavenger receptor and fatty acid translocase, is upregulated in peripheral blood mononuclear cells (PBMCs) among patients with type 2 diabetes and is a biomarker of PBMC activation and inflammation. RESEARCH DESIGN AND METHODS We used a cross-sectional observational design to study a multi-racial/ethnic population sample consisting of Caucasians, Hispanics, and Native Americans with type 2 diabetes (n = 33) and nondiabetic control subjects (n = 27). PBMC CD36 mRNA/protein and plasma high sensitivity (hs) C-reactive protein (hsCRP), hs–interleukin-6 (hsIL-6), and adiponectin were measured. RESULTS Unadjusted PBMC CD36 mRNA and protein were 1.56- and 1.63-fold higher, respectively, among type 2 diabetic subjects versus control subjects. PBMC CD36 protein was directly associated with CD36 mRNA, plasma hsCRP, and hsIL-6 and inversely associated with plasma adiponectin in both groups. CONCLUSIONS Increased CD36 expression is a biomarker of PBMC activation and inflammation and may become a useful tool in cardiovascular disease risk stratification.

Effects of kelp supplementation on thyroid function in euthyroid subjects.

OBJECTIVE To study the effects of ingestion of two different doses of supplemental kelp on the thyroid function of healthy euthyroid subjects. METHODS We conducted a double-blind prospective clinical trial involving 36 healthy euthyroid subjects, who were randomly assigned to receive placebo (4 alfalfa capsules per day), low-dose kelp (2 kelp capsules and 2 alfalfa capsules per day), or high-dose kelp (4 kelp capsules per day) for 4 weeks. Thyrotropin (thyroid-stimulating hormone or TSH), free thyroxine, and total triiodothyronine were assessed at weeks 0, 4, and 6. Response to thyrotropin-releasing hormone stimulation, urinary iodine excretion, and basal metabolic rate were determined at weeks 0 and 4. RESULTS TSH concentrations did not differ significantly between week 0 and week 4 in the placebo group (P = 0.16) but increased significantly in both the low-dose kelp (P = 0.04) and high-dose kelp (P = 0.002) groups. Free thyroxine concentrations decreased slightly but significantly after 4 weeks of placebo but were unchanged in the low-dose and the high-dose kelp groups. In contrast, total triiodothyronine levels did not differ significantly after 4 weeks of placebo or low-dose kelp therapy but were significantly decreased after high-dose kelp therapy (P = 0.04). Similarly, the thyrotropin-releasing hormone stimulation test showed no significant change in poststimulation TSH after 4 weeks in the placebo or low-dose kelp groups but revealed a significantly increased response after high-dose kelp therapy (P = 0.0002). The 24-hour urinary iodine excretion showed dose-dependent increases in the two kelp study groups. Basal metabolic rate did not change significantly in any study group during the 4-week study period. All thyroid laboratory values returned to baseline 2 weeks after cessation of kelp supplementation, except for TSH in the high-dose kelp group, which was significantly decreased. CONCLUSION Short-term dietary supplementation with kelp significantly increases both basal and poststimulation TSH. These findings corroborate previous studies on the effects of supplemental iodide given to euthyroid subjects for a similar period. Further studies are needed to determine whether long-term kelp supplementation would cause clinically significant thyroid disease.