Effect of a diabetes order set on glycaemic management and control in the hospital.

PROBLEM: Insulin can have favourable effects on patient outcomes when used appropriately; however, it is considered among the top five medications associated with errors in the hospital setting. SETTING: Tertiary care centre. METHODS: A diabetes order set with prescribing guidelines was developed by a multidisciplinary diabetes patient safety committee, and introduced on an inpatient unit (the order set unit) following educational sessions with doctors/nurses. To determine the safety and efficacy of the order set, all orders for diabetes medications on patients with 3 days of bedside blood glucose data were recorded and reviewed for types and appropriateness of orders and compared with those written on a unit not using the order set (control unit). An expert panel not involved in the project reviewed and determined appropriateness according to criteria that included evidence of insulin adjustments for hyperglycaemia, hypoglycaemia, or steroid therapy. Satisfaction with the order set among clinical personnel was elicited by a four-item questionnaire. RESULTS: There were more orders for scheduled basal/bolus insulin therapy (p = 0.008) and fewer orders for correctional insulin alone on the order set unit than the control unit. A trend toward more appropriate orders (91% vs 80%) was observed on the order set unit. A high degree of satisfaction for the diabetes order set was elicited from doctors, nurse practitioners, nurses and clerical staff using a four-item survey. CONCLUSIONS: A diabetes order set with prescribing guidelines can safely and effectively be implemented in hospitals. The success of this intervention is attributed to the contribution of nurses, pharmacists and prescribers in the design and implementation of the order set, the provider education accompanying order set implementation and the feedback following implementation.

Use of a standardized protocol to decrease medication errors and adverse events related to sliding scale insulin.

PROBLEM: Sliding scale insulin (SSI) is frequently used for inpatient management of hyperglycemia and is associated with a large number of medication errors and adverse events including hypoglycemia and hyperglycemia. DESIGN: Observational before and after study evaluating the impact of implementation of a standardized SSI protocol and preprinted physician order form. SETTING: University Hospital in Pittsburgh, PA, USA. STRATEGY FOR CHANGE: Guidelines for the use of SSI were created by an interdisciplinary committee and implemented in non-intensive care units. In addition, a preprinted physician order sheet was developed which included the guidelines and an option for ordering one of three standardized insulin sliding scales or a patient specific scale. EFFECT OF CHANGE: One year after implementation the physician order form was used for 91% of orders and, overall, 86% of SSI orders followed the guidelines. The number of prescribing errors found on chart review was reduced from 10.3 per 100 SSI patient-days at baseline to 1.2 at 1 year (p = 0.03). The number of hyperglycemia episodes 1 year after implementation decreased from 55.9 to 16.3 per 100 SSI patient-days. LESSONS LEARNT: The protocol was readily accepted by hospital staff and was associated with decreased prescribing errors and decreased frequency of hyperglycemia.

Is type 2 diabetes a chronic inflammatory/autoimmune disease?

The classification of diabetes mellitus into 2 main types, defined as Type 1 and 2 diabetes (T1DM, T2DM) relies mostly on the requirement of insulin therapy and on the presence of detectable immunologic abnormalities. However, this distinction is far from straightforward and there is considerable overlap between these 2 types of diabetes. Islet cell autoimmunity, which is characteristic of T1DM, appears in fact to be present in up to 10-15% of subjects diagnosed clinically with T2DM. In the UK Prospective Diabetes Study (UKPDS), it was reported that in patients diagnosed with in T2DM, the presence of autoantibodies to the enzyme glutamic acid decarboxylase (GAD) and cytoplasmic islet cell antibodies (ICA) were a predictor of insulin requirement as compared with patients not carrying these autoantibodies. These results are strikingly similar to a number of prospective studies carried out in childhood diabetes. If islet cell autoimmunity is truly present in 10-15% of subjects clinically diagnosed with T2DM, up to two million Americans might have an unidentified autoimmune form of T2DM, a prevalence similar to that of recent onset childhood diabetes. In addition, we found that in a subset of T2DM patients, a pronounced activation of the acute phase response that seems to be associated with islet cell autoimmunity. These results may in part explain the defect in insulin secretion as well as insulin resistance seen in T2DM. The identification of a subgroup of individuals at risk of developing T2DM using autoantibody as well as inflammatory markers is of public health interest, not only for the correct classification of diabetes, but also because immunomodulatory therapeutic strategies could potentially be instituted sufficiently early in a large number of patients diagnosed as having T2DM and most likely delay the onset of insulin requirement and the complications related with hyperglycemia.

FABP2 genotype is associated with insulin sensitivity in older women.

This study determined whether sequence variations in genes related to glucose and insulin metabolism are associated with insulin sensitivity in postmenopausal women after accounting for habitual physical activity levels, body composition, and hormone-replacement therapy (HRT). Eighteen sedentary, 19 physically active, and 23 athletic postmenopausal white women underwent a frequently sampled intravenous glucose tolerance test to determine insulin sensitivity (S(I)) and dual-energy x-ray absorptiometry to determine body composition. After accounting for the effects of body composition, habitual physical activity levels, and HRT status, S(I) was 26% lower in subjects with the Thr54 fatty acid-binding protein 2 (FABP2) allele compared with Ala54 homozygotes (4.3 +/- 0.5 v 5.8 +/- 0.6 microU x 10(-4)/min/mL; P <.05). Angiotensin-converting enzyme genotype was not significantly associated with S(I). There were no significant associations between Gln27Glu beta(2)-adrenergic receptor or Pro12Ala peroxisome proliferator-activated receptor gamma variants and glucose or insulin kinetic parameters. It was concluded that FABP2 genotype influences insulin sensitivity independent of body composition, habitual physical activity levels, and HRT status in postmenopausal white women.

Insulin sensitivity in postmenopausal women: independent and combined associations with hormone replacement, cardiovascular fitness, and body composition.

OBJECTIVE: The effects of combined physical activity and hormone replacement therapy (HRT) on insulin sensitivity in postmenopausal (PM) women are unclear. The purpose of the study was to test the following hypotheses: 1) PM women who have undergone vigorous exercise training have greater insulin sensitivity than PM women who are physically active and PM women who are sedentary, and 2) PM women using HRT have greater insulin sensitivity than PM women not using HRT. We also sought to determine whether body composition or cardiovascular fitness was the stronger predictor of insulin sensitivity in these women. RESEARCH DESIGN AND METHODS: Three groups of PM women classified as sedentary (n = 18), physically active (n = 19), and athletic (n = 23) underwent an insulin-modified frequently sampled intravenous glucose tolerance test to determine the insulin sensitivity index (SI) and dual-energy X-ray absorptiometry to determine body composition. RESULTS: There was a significant association between both physical activity (P = 0.036) and HRT (P = 0.007) and fasting plasma insulin levels. The athletic PM women had the lowest plasma insulin levels and the highest SI. Across all physical activity levels, PM women using HRT (n = 29) had significantly lower fasting plasma insulin levels and a lower SI than PM women not using HRT (n = 31). HRT was significantly (P = 0.025) associated with intravenous glucose tolerance (KG); the women not using HRT had a higher K(G); than the PM women using HRT (0.83 +/- 0.08 vs. 0.60 +/- 0.05% per minute). Percent body fat (r = -0.37, P = 0.004) and VO2max (r = 0.35, P = 0.007) were similar predictors of SI. CONCLUSIONS: We conclude that, although overall HRT was associated with an attenuated SI, vigorous exercise training was independently associated with the greatest SI. In addition, PM women using HRT may benefit from having lower plasma insulin levels, but they may also have a lower SI.

Reduced beta-adrenergic sensitivity in patients with type 1 diabetes and hypoglycemia unawareness.

OBJECTIVE: We tested the hypothesis that impaired tissue sensitivity to catecholamines contributes to hypoglycemia unawareness in subjects with type 1 diabetes. RESEARCH DESIGN AND METHODS: A total of 21 subjects with type 1 diabetes underwent a standardized insulin infusion protocol to produce a stepwise decrease in plasma glucose to 45-min plateaus of 4.3, 3.6, 3.0, and 2.3 mmol/l. Glycemic thresholds, maximum responses for adrenergic and neuroglycopenic symptoms, and counterregulatory hormones were determined. Patients were classified as hypoglycemia unaware if the initiation of adrenergic symptoms occurred at a plasma glucose level 2 SD below that of nondiabetic volunteers. beta-Adrenergic sensitivity was measured as the dose of isoproterenol required to produce an increment in heart rate of 25 beats per minute above baseline (I25) in resting subjects. RESULTS: Subjects with type 1 diabetes and hypoglycemia unawareness experienced the onset of adrenergic symptoms at a lower plasma glucose level than did those with awareness (2.5+/-0.1 vs. 3.7+/-0.1 mmol/l, P < 0.001), whereas neuroglycopenic symptoms occurred at similar glucose levels (2.7+/-0.2 vs. 2.8+/- 0.1 mmol/l). The plasma glucose levels for counterregulatory hormone secretion (epinephrine 2.9+/-0.2 vs. 4.1+/-0.2 mmol/l; norepinephrine 2.7+/-0.1 vs. 3.2+/-0.2 mmol/l; cortisol 2.5+/-0.2 vs. 3.3+/-0.2 mmol/l, P < 0.01) were also lower in subjects with unawareness. The maximal epinephrine (1,954+/-486 vs. 5,332+/- 1,059 pmol/l, P < 0.01), norepinephrine (0.73 +/- 0.14 vs. 1.47+/-0.21 nmol/l, P = 0.04), and cortisol (276+/-110 vs. 579+/-83 nmol/l, P < 0.01) responses were reduced in the unaware group. I25 was greater in unaware subjects than in subjects without unawareness (1.5+/-0.3 vs. 0.8+/-0.2 microg), where I25 was not different from that of controls (0.8 +/-0.2 microg). CONCLUSIONS: We conclude that subjects with type 1 diabetes and hypoglycemia unawareness have reduced beta-adrenergic sensitivity, which may contribute to their impaired adrenergic warning symptoms during hypoglycemia.

Improvement of insulin sensitivity by short-term exercise training in hypertensive African American women.

African American women have a high prevalence of insulin resistance, non-insulin-dependent diabetes mellitus, obesity, and hypertension that may be linked to low levels of physical activity. We sought to determine whether 7 days of aerobic exercise improved glucose and insulin metabolism in 12 obese (body fat >35%), hypertensive (systolic blood pressure > or =140 and/or diastolic blood pressure > or =90 mmHg) African American women (mean age 51+/-8 years). Insulin-assisted frequently-sampled intravenous glucose tolerance tests were performed at baseline and 14 to 18 hours after the 7th exercise session. There was no significant change in maximal oxygen consumption, body composition, or body weight after the 7 days of aerobic exercise. The insulin sensitivity index increased (2.68+/-0.45 x 10[-5] to 4.23+/-0.10 x 10[-5] [min(-1)/pmol/L], P=.02). Fasting (73+/-9 to 50+/-9 pmol/L, P=.02) and glucose-stimulated (332+/-58 to 261+/-45 pmol/L, P=.05) plasma insulin levels decreased. Additional measures related to the insulin resistance syndrome also changed with the 7 days of exercise: basal plasma norepinephrine concentrations were reduced (2.46+/-0.27 to 1.81+/-0.27 nmol/L, P=.02) and sodium excretion rate increased from 100+/-13 to 137+/-7 mmol/d (P=.03); however, there was no change in potassium excretion or 24-hour ambulatory blood pressure. We conclude that a short-term aerobic exercise program improves insulin sensitivity in African American hypertensive women independent of changes in fitness levels, body composition, or body weight. The present study indicates that short-term exercise can improve insulin resistance in hypertensive, obese, sedentary African American women and confirms previous reports that a portion of the exercise-induced improvements in glucose and insulin metabolism may be the result of recent exercise.

Spectrum of malignancy and premalignancy in Carney syndrome.

Carney syndrome is a rare, autosomal dominant, multi-system disorder comprising 8 well-characterized findings, only 2 of which need be present for a definitive diagnosis. Benign neoplasms are frequent, but malignancies are thought to be uncommon. We have studied a family to clarify the diagnosis and spectrum of clinical manifestations of the syndrome and to develop guidelines for management. The proposita, a 34-year-old woman had classic findings of Carney syndrome, invasive follicular carcinoma of the thyroid gland, Barrett metaplasia of the esophagus, neoplastic colonic polyps, bipolar affective disorder, and atypical mesenchymal neoplasm of the uterine cervix distinct from the myxoid uterine leiomyoma usually seen in this syndrome. Although thyroid gland neoplasm is rare in Carney syndrome, this patient's most aggressive manifestation was her thyroid carcinoma. The diagnosis of Carney syndrome was established in her 9-year-old son and is a probable diagnosis in her 12-year-old daughter. Endocrine manifestations were prominent in the family with at least 9 relatives in 3 generations affected with various endocrine abnormalities. The findings in this family indicate that the spectrum of manifestations in this pleiotropic gene apparently includes a malignant course with premalignant and endocrinologic disorders not previously recognized.

Metabolic effects of oral contraceptives in women with polycystic ovary syndrome.

Insulin resistance and dyslipidemia have been described in women with polycystic ovary syndrome (PCOS), a disorder characterized by hyperandrogenism and oligomenorrhea. Although oral contraceptives (OC) are often instituted to regulate menses and suppress HA in women with PCOS, their use has been postulated to cause a deterioration in insulin sensitivity and to adversely affect circulating lipids. To investigate these effects, 9 women with PCOS and 10 age- and weight-matched control women were studied before and during the third month of therapy with a low-dose norethindrone-containing triphasic combination OC using the hyperglycemic clamp technique. At baseline, the PCOS group had higher androgen, triglyceride, and glycosylated hemoglobin concentrations, with a greater insulin response to oral glucose and a lower insulin sensitivity index (ISI) than controls. During OC therapy, a reduction in ISI was observed in both groups, whereas an increase in triglycerides was observed only in controls, removing any observed difference between the two groups in ISI or lipids. In women with PCOS, an increase in insulin concentrations during hyperglycemia accounted for the decline in ISI (P = 0.026), whereas in control women the decrease in ISI was attributable to a decrease in glucose disposal (P = 0.004). In conclusion, PCOS is characterized by insulin resistance in the untreated state. Short-term therapy with a triphasic OC results in a further decline in ISI in women with PCOS, without inducing additional adverse effects on lipids. A more pronounced decline in ISI together with an elevation in triglyceride levels occurs in normal women with OCs. The mechanisms leading to this decrease in ISI are different for each group.

Comparison of the minimal model and the hyperglycemic clamp for measuring insulin sensitivity and acute insulin response to glucose.

Glucose clamp techniques are established methods for assessment of insulin sensitivity and secretion. The minimal model technique (MMT) has been proposed as an alternative approach to the hyperinsulinemic-euglycemic clamp technique for determination of an insulin sensitivity index (ISI), but has not been directly compared with the hyperglycemic clamp for measurement of ISI or insulin secretion. To address this issue, the present study was undertaken to compare determinations of ISI and the acute insulin response to glucose (AIRg) obtained using the MMT with similar measures obtained from a hyperglycemic clamp. Measures for ISI and AIRg obtained from MMT analysis of a tolbutamide-modified frequently sampled intravenous glucose tolerance test (FSIGT) were compared with similar measures obtained from a 3-hour hyperglycemic clamp performed at a plasma glucose level of 10 mmol/L (180 mg/dL). Paired comparisons were performed in 14 women with normal glucose tolerance. Significant positive correlation coefficients were obtained for both ISI (r = .88, P < .001) and AIRg (r = .75, P < .005) between the MMT and clamp studies. We conclude that indices for ISI and AIRg obtained with the MMT are highly correlated with those obtained using the hyperglycemic clamp. The MMT is a valid alternative to the hyperglycemic clamp for assessing insulin sensitivity and AIRg.

Age-related changes in basal and sodium-stimulated atrial and plasma atrial natriuretic factor (ANF) in the rat.

To examine effects of age on basal and sodium-stimulated plasma concentrations and atrial contents of atrial natriuretic factor (ANF), young (2 mo), mature (4 mo), and older adult (12-18 mo) rats were maintained on a low-sodium diet (less than .05% by weight) for 8 days. Half of each group then received a high-sodium diet (3.1%) for 24 hours before sacrifice. Mean plasma ANF concentrations were greater in the older adult rats, 506 +/- 287 pg/ml, than in young or mature rats, 262 +/- 182 and 150 +/- 40 pg/ml, respectively (p less than .001). Age-related increases in plasma ANF concentration and left atrial ANF content (p less than .001) were present in both low- and high-sodium fed rats. Significant differences in plasma and atrial ANF levels between low- and high-sodium fed rats were noted only in older adult rats, where an inverse correlation (r = -.425, p less than .05) was observed between plasma and left atrial ANF levels. These observations demonstrate that plasma and atrial ANF levels increase with age in the rat. With aging, increased ANF effects may modulate other systems regulating cardiovascular homeostasis.