Treatment approaches and costs associated with diabetes clinical metrics as measured by Healthcare Effectiveness Data and Information Set (HEDIS).

BACKGROUND: The clinical outcomes of diabetes can be influenced by primary care providers' (PCP) treatment approaches. This study explores the association between PCP approaches to management and performance measured by established diabetes metrics and related costs. METHODS: In phase one, Electronic Medical Records were used to extract diabetes related metrics using Healthcare Effectiveness Data and Information Set (HEDIS), for patients with diabetes who had office visits to 44 PCP practices from April 2019 to March 2020. Using those metrics and scoring system, PCP practices were ranked and then categorized into high- and low-performing groups (top and bottom 25%, n = 11 each), with a total of 19,059 clinic visits by patients with a diagnosis of diabetes. Then extensive analysis was performed to evaluate a correlation between treatment approaches and diabetes outcomes across the top and bottom performing practices. In phase 2, patients with diabetes who were attributed to the aforementioned PCP practices were identified in a local health plan claims data base (a total of 3,221 patients), and the allowed amounts from their claims were used to evaluate differences in total and diabetes-related healthcare costs by providers' performance. RESULTS: Comparing 10,834 visits in high-performing practices to 8,235 visits in low-performing practices, referrals to certified diabetes care and education specialists and provider-to-provider electronic consults (e-consults) were higher in high-performing practices (Z = 6.06, p < .0001), while traditional referrals were higher in low-performing practices (Z = -6.94, p < .0001). The patient-to-provider ratio was higher in the low-performing group (M = 235.23) than in the high-performing group (M = 153.26) (Z = -2.82, p = .0048). Claims data analysis included 1,825 and 1,396 patients from high- and low-performing providers, respectively. The patient-to-provider ratio was again higher in the low-performing group (p = .009, V = 0.62). Patients receiving care from lower-performing practices were more likely to have had a diabetes-related hospital observation (5.7% vs. 3.9%, p = .02; V = 0.04) and higher diabetes-related care costs (p = .002; d = - 0.07); these differences by performance status persisted when controlling for differences in patient and physician characteristics. Patients seeing low-performing providers had higher Charlson Comorbidity Index scores (Mdn = 3) than those seeing high-performing providers (Mdn = 2). CONCLUSIONS: Referrals to the CDCES and e-Consult were associated with better measured diabetes outcomes, as were certain aspects of cost and types of hospital utilization. Higher patients to providers ratio and patients with more comorbidities were observed in low performing group.

Experimental pharmacological approaches to reverse impaired awareness of hypoglycemia-a review.

The colossal global burden of diabetes management is compounded by the serious complication of hypoglycemia. Protective physiologic hormonal and neurogenic counterregulatory responses to hypoglycemia are essential to preserve glucose homeostasis and avert serious morbidity. With recurrent exposure to hypoglycemic episodes over time, these counterregulatory responses to hypoglycemia can diminish, resulting in an impaired awareness of hypoglycemia (IAH). IAH is characterized by sudden neuroglycopenia rather than preceding cautionary autonomic symptoms. IAH increases the risk of subsequent sudden and severe hypoglycemic episodes in patients with diabetes. The postulated causative mechanisms behind IAH are complex and varied. It is therefore challenging to identify a single effective therapeutic strategy. In this review, we closely examine the efficacy and feasibility of a myriad of pharmaceutical interventions in preventing and treating IAH as described in clinical and preclinical studies. Pharmaceutical agents outlined include N-acetyl cysteine, GABA A receptor blockers, opioid receptor antagonists, AMP activated protein kinase agonists, potassium channel openers, dehydroepiandrosterone, metoclopramide, antiadrenergic agents, antidiabetic agents and glucagon.

A Randomized Controlled Trial Comparing Glargine U300 and Glargine U100 for the Inpatient Management of Medicine and Surgery Patients With Type 2 Diabetes: Glargine U300 Hospital Trial.

OBJECTIVE: The role of U300 glargine insulin for the inpatient management of type 2 diabetes (T2D) has not been determined. We compared the safety and efficacy of glargine U300 versus glargine U100 in noncritically ill patients with T2D. RESEARCH DESIGN AND METHODS: This prospective, open-label, randomized clinical trial included 176 patients with poorly controlled T2D (admission blood glucose [BG] 228 ± 82 mg/dL and HbA1c 9.5 ± 2.2%), treated with oral agents or insulin before admission. Patients were treated with a basal-bolus regimen with glargine U300 (n = 92) or glargine U100 (n = 84) and glulisine before meals. We adjusted insulin daily to a target BG of 70-180 mg/dL. The primary end point was noninferiority in the mean difference in daily BG between groups. The major safety outcome was the occurrence of hypoglycemia. RESULTS: There were no differences between glargine U300 and U100 in mean daily BG (186 ± 40 vs. 184 ± 46 mg/dL, P = 0.62), percentage of readings within target BG of 70-180 mg/dL (50 ± 27% vs. 55 ± 29%, P = 0.3), length of stay (median [IQR] 6.0 [4.0, 8.0] vs. 4.0 [3.0, 7.0] days, P = 0.06), hospital complications (6.5% vs. 11%, P = 0.42), or insulin total daily dose (0.43 ± 0.21 vs. 0.42 ± 0.20 units/kg/day, P = 0.74). There were no differences in the proportion of patients with BG <70 mg/dL (8.7% vs. 9.5%, P > 0.99), but glargine U300 resulted in significantly lower rates of clinically significant hypoglycemia (<54 mg/dL) compared with glargine U100 (0% vs. 6.0%, P = 0.023). CONCLUSIONS: Hospital treatment with glargine U300 resulted in similar glycemic control compared with glargine U100 and may be associated with a lower incidence of clinically significant hypoglycemia.

Glycemic Control in Hospitalized Patients with Diabetes Receiving Corticosteroids Using a Neutral Protamine Hagedorn Insulin Protocol: A Randomized Clinical Trial.

INTRODUCTION: Hospitalized patients with diabetes receiving corticosteroids are at risk of developing hyperglycemia and related complications. This study evaluated a neutral protamine Hagedorn (NPH) insulin-based protocol in improving glycemic control in hospitalized patients receiving corticosteroids. METHODS: This was a randomized, prospective, non-blinded study in an inpatient setting involving patients with diabetes who were hospitalized and receiving prednisone ≥ 10 mg per day or equivalent. High dose corticosteroids group (prednisone > 40 mg/day or equivalent) received NPH insulin 0.3 U/kg between 0600 and 2000 hours if eating or 0.2 U/kg between 2000 and 0600 hours if not eating. Low dose corticosteroids group (prednisone 10-40 mg/day or equivalent) received 0.15 U/kg between 0600 and 2000 hours if eating or 0.1 U/kg between 2000 and 0600 hours if not eating. Primary outcome measure was mean blood glucose level measured pre-meal and at bedtime for days 1-5. RESULTS: Mean blood glucose level was lower in the intervention (n = 29) than in the usual care (n = 31) group [226.12 vs. 268.57 mg/dL, respectively, (95% CI for difference - 63.195 to - 21.695), p < 0.0001]. Significant differences in mean glucose level were noted at fasting [170.96 vs. 221.13 mg/dL, respectively, (95% CI for difference - 72.70 to - 27.63), p < 0.0001] and pre-lunch [208 vs. 266.48 mg/dL, respectively, (95% CI for difference - 86.61 to - 30.36), p < 0.0001]. CONCLUSION: In hospitalized patients with diabetes receiving corticosteroids, an NPH insulin-based protocol improves glycemic control. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT01970241. FUNDING: Eli Lilly and Company.

Duration and onset of action of high dose U-500 regular insulin in severely insulin resistant subjects with type 2 diabetes.

AIM: Although regular human U-500 insulin (U-500) is frequently used for insulin resistant type 2 diabetics, pharmacokinetic and pharmacodynamic studies in these individuals are lacking. We set out to determine the rate of onset, duration of action and total glucose lowering effect of two doses of U-500 insulin in obese insulin resistant subjects with type 2 diabetes. MATERIALS AND METHODS: Randomized double-blind crossover study was designed to study subjects who were administered either 100 or 200 units SQ of U-500 insulin once and then were provided intravenous glucose as necessary to maintain euglycaemia. RESULTS: A total of 12 subjects were studied. The time during which intravenous glucose was required to maintain euglycaemia following a 200-unit dose of U-500 insulin was significantly greater than the time following a 100-unit dose. No differences were found between doses in measures related to the rate of onset or in the total amount of intravenous glucose required to maintain euglycaemia for the duration of the study. CONCLUSIONS: The duration of action of U-500 increases when dose is increased from 100 to 200 units. Neither dose of U-500 insulin has an onset of action before 2.5 hours after administration. This suggests that U-500 should not be used as a premeal bolus insulin to lower glucose two hours after a meal and that dosing intervals might need to be extended as dose is increased to avoid hypoglycaemia.

Cerebral glycogen in humans following acute and recurrent hypoglycemia: Implications on a role in hypoglycemia unawareness.

Supercompensated brain glycogen levels may contribute to the development of hypoglycemia-associated autonomic failure (HAAF) following recurrent hypoglycemia (RH) by providing energy for the brain during subsequent periods of hypoglycemia. To assess the role of glycogen supercompensation in the generation of HAAF, we estimated the level of brain glycogen following RH and acute hypoglycemia (AH). After undergoing 3 hyperinsulinemic, euglycemic and 3 hyperinsulinemic, hypoglycemic clamps (RH) on separate occasions at least 1 month apart, five healthy volunteers received [1-13C]glucose intravenously over 80+ h while maintaining euglycemia. 13C-glycogen levels in the occipital lobe were measured by 13C magnetic resonance spectroscopy at ∼8, 20, 32, 44, 56, 68 and 80 h at 4 T and glycogen levels estimated by fitting the data with a biophysical model that takes into account the tiered glycogen structure. Similarly, prior 13C-glycogen data obtained following a single hypoglycemic episode (AH) were fitted with the same model. Glycogen levels did not significantly increase after RH relative to after euglycemia, while they increased by ∼16% after AH relative to after euglycemia. These data suggest that glycogen supercompensation may be blunted with repeated hypoglycemic episodes. A causal relationship between glycogen supercompensation and generation of HAAF remains to be established.

In vivo Magnetic Resonance Spectroscopy of cerebral glycogen metabolism in animals and humans.

Glycogen serves as an important energy reservoir in the human body. Despite the abundance of glycogen in the liver and skeletal muscles, its concentration in the brain is relatively low, hence its significance has been questioned. A major challenge in studying brain glycogen metabolism has been the lack of availability of non-invasive techniques for quantification of brain glycogen in vivo. Invasive methods for brain glycogen quantification such as post mortem extraction following high energy microwave irradiation are not applicable in the human brain. With the advent of (13)C Magnetic Resonance Spectroscopy (MRS), it has been possible to measure brain glycogen concentrations and turnover in physiological conditions, as well as under the influence of stressors such as hypoglycemia and visual stimulation. This review presents an overview of the principles of the (13)C MRS methodology and its applications in both animals and humans to further our understanding of glycogen metabolism under normal physiological and pathophysiological conditions such as hypoglycemia unawareness.

Hypoglycemia mediated by paraneoplastic production of Insulin like growth factor-2 from a malignant renal solitary fibrous tumor - clinical case and literature review.

BACKGROUND: Hypoglycemic episodes are infrequent in individuals without a history of diabetes mellitus or bariatric surgery. When hypoglycemia does occur in such individuals, an uncommon but important diagnosis to consider is non-islet cell tumor hypoglycemia (NICTH). We report a case of NICTH associated with paraneoplastic insulin-like growth factor-2 (IGF-2) production and review current relevant medical literature. CASE PRESENTATION: A 60 year old male with no relevant past medical history was referred to the endocrinology clinic with 18 month history of episodic hypoglycemic symptoms and, on one occasion was noted to have a fingerstick glucose of 36 mg/dL while having symptoms of hypoglycemia. Basic laboratory evaluation was unrevealing. Further evaluation however showed an elevated serum IGF-2 level at 2215 ng/mL (reference range 411-1248 ng/mL). Imaging demonstrated a large right suprarenal mass. A right nephrectomy with resection of the mass demonstrated a malignant solitary fibrous tumor. Post resection, the patient's IGF-2 levels normalized and hypoglycemic symptoms resolved. CONCLUSION: Due to the structural and biochemical homology between IGF-2 and insulin, elevated levels of IGF-2 can result in hypoglycemia. A posttranslational precursor to IGF-2 known as "big IGF" also possesses biologic activity. Review of recent reported cases of NICTH identified widespread anatomic locations and varied pathologic diagnoses of tumors associated with paraneoplastic production of IGF-2 causing hypoglycemia. Definitive management of hypoglycemia associated with paraneoplastic production of IGF-2 consists of resection of the tumor responsible for IGF-2 production. Accumulating literature provides a firm basis for routine IGF-2 laboratory evaluation in patients presenting with spontaneous hypoglycemia with no readily apparent cause.

Assessment of asthma control using the asthma control test at a tertiary care centre in Karachi, Pakistan.

The aim of our study was to assess asthma control among asthmatics at a tertiary care setting in Karachi using ACT questionnaire. The ACT questionnaire was filled by known asthmatics in January 2007. A total of 150 questionnaires were filled of which, 61 (40%) were males and 89 (60%) females. Mean ACT score was 17.71 +/- 4.41. Association between sex and asthma control was not statistically significant. Significant association was seen with asthma control and Ipratropium bromide inhaler. Asthma control among patients at a tertiary care centre is moderate. ACT can be used to follow patients in the hospital.

Extrapleural hydatid disease of chest: a case of recurrent hydatid disease.

Hydatid disease is a parasitic infestation by a tapeworm of the genus Echinococcus. We present the case of 34-year-old female who complained of chest pain and had a past history of hydatid cyst resection four times in last 15 years. She was found to have extrapleural hyatid cysts of chest that were removed via thoracotomy. The patient fully recovered and experienced an uneventful follow-up.

Rhabdomyosarcoma embryonal type: in a three and a half year old girl.

Rhadomyosarcoma is the most common tumour of the soft tissues in infants and children. We report a case of a 3 1/2 year old girl who presented with a swelling over the neck. Swelling was diagnosed as Rhabdomyosarcoma (embryonal type). Tumour mass was found to be unresectable initially. The patient was subjected to multiple courses of checmotherapy, which shrunk the tumour significantly. There was simultaneous development of cystic lesions in upper lobe of right lung. Excision of the remnant rhabdomyosarcoma mass and biopsy of right lung with cystectomy of right upper lobe cystic lesion was performed. The patient fully recovered and experienced an uneventful 6 months of follow-up.

Extensive primary malignant thymoma involving pericardium, pleura, diaphragm and lungs--a case report.

Malignant thymoma is an extremely rare entity. According to a study, the annual incidence of malignant thymoma was estimated to be 0.15 per 100,000 person-years. We present the case of a 42-year-old female who came to us with a Type AB, Masaoka stage III malignant (invasive) thymoma with widespread involvement of the mediastinum.

Chylopericardium--a rare complication after ventricular septal defect repair.

Chylopericardium is a rare complication of cardiac surgery. It may be caused by a lesion in the thoracic duct or its tributaries or by thrombosis in the confluence of the jugular and left subclavian veins, obstructing the drainage of the thoracic duct. The treatment may be conservative or surgical, depending on the duration and on the volume of the effusion. We report the case of a 1 1/2 year-old male, who, in the late postoperative period of VSD repair, was hospitalized with low-grade fever and breathlessness for one week due to the presence of chylopericardium. The clinical findings and treatment performed are discussed.