Hypoglycemia in Patients with Type 2 Diabetes Mellitus and Chronic Kidney Disease: A Prospective Observational Study.

Background: Glycemic management in patients with type 2 diabetes mellitus (T2DM) and CKD can become complicated. One factor that may affect treatment is hypoglycemia. Hypoglycemia risk may be increased by several biologic processes in CKD. The objective of this study was to determine the frequency, severity, and risk factors for hypoglycemia in patients with T2DM and CKD. Methods: The design was a prospective observational study. A continuous glucose monitor (CGM) was worn by 80 patients for up to 14 days; glucose was measured every 15 minutes. Patients with T2DM and eGFR <45 ml/min were enrolled. Patients on dialysis were excluded. The primary outcome was to assess the frequency of hypoglycemic episodes during the study period. Hypoglycemic episodes were defined as a reduced glucose concentration (<70 mg/dl) lasting ≥15 minutes. Secondary outcomes included assessment of severity of hypoglycemia and risk factors for its development. Results: A total of 80 patients wore the CGM for a mean of 12.7±2.9 days. Hypoglycemic events occurred in 61 of 80 patients (76%) with glucose <70 mg/dl, and 49 of 80 (61%) with glucose <60 mg/dl. Prolonged hypoglycemic events (CGM glucose <54 mg/dl for ≥120 consecutive minutes) occurred in 31 patients (39%) with 118 total events. Most hypoglycemic episodes occurred overnight, from 1:00 am to 9:00 am. By multivariate analysis, lower hemoglobin A1c and treatment with insulin were two modifiable risk factors for hypoglycemic events. Conclusions: Patients with T2DM and CKD have frequent periods of hypoglycemia that can be severe and prolonged. Hemoglobin A1c does not portray the full scope of hypoglycemia risk. This study illustrates the need for careful monitoring of glucose levels in patients with T2DM and CKD.

Continuous Glucose Monitoring and Glycemic Control in Patients With Type 2 Diabetes Mellitus and CKD.

RATIONALE & OBJECTIVE: The accuracy of glycated hemoglobin (HbA1c) level for assessment of glycemic control in patients with chronic kidney disease (CKD) is uncertain. This study assessed the accuracy of HbA1c level using continuous glucose monitoring. STUDY DESIGN: Diagnostic test study of HbA1c and serum fructosamine. The continuous glucose monitor was worn for 14 days. Glucose was measured every 15 minutes (up to 1,344 measurements). Average glucose concentration was calculated for each patient from the patient's continuous glucose monitor measurements. Linear regression was applied to estimate the relationship between average glucose concentration and HbA1c and serum fructosamine levels. The influence of patient characteristics on the relationship between HbA1c and average glucose concentrations was examined in a multivariate regression model. SETTING & PARTICIPANTS: Patients with type 2 diabetes and CKD (estimated glomerular filtration rate, 7-45 mL/min, not receiving dialysis) seen in an academic nephrology clinic. TESTS ANALYZED: The accuracy of HbA1c level for assessment of chronic glycemia. A secondary objective was to study serum fructosamine levels. OUTCOMES: The degree of correlation between continuous glucose monitoring-derived average glucose concentration and HbA1c level; serum fructosamine level was studied as a secondary outcome. RESULTS: 80 patients wore the continuous glucose monitor for a mean of 12.7 ± 2.9 days. Average glucose concentration of all patients was 151.5 ± 55.7 mg/dL. Mean HbA1c level was 7.2% ± 1.5%. HbA1c level was highly correlated with average glucose concentration, described by the equation: average glucose concentration = 30.48 × HbA1c - 68.48; r = 0.82; P < 0.001. Serum fructosamine level was also significantly correlated with average glucose concentration; r = 0.55; P < 0.001. The strong correlation between average glucose concentration and HbA1c level was not affected by the severity of CKD, whereas the performance of serum fructosamine level, in contrast, degraded among patients with more severe CKD. LIMITATIONS: Relatively small sample size. CONCLUSIONS: HbA1c is an accurate measure of glycemic status among patients with CKD and type 2 diabetes. This relationship appears to hold true among patients with more severe CKD.

Hypercalcemia of Malignancy and Colorectal Cancer.

Our aim is to describe the association between colorectal cancer (CRC) and humoral hypercalcemia of malignancy (HHM). Causes of hypercalcemia of malignancy include parathyroid hormone-related peptide (PTHrP) secretion, local osteolysis, calcitriol production and ectopic parathyroid hormone (PTH) secretion. Hypercalcemia of malignancy in patients with CRCs is a rare scenario. A patient with anal squamous cell carcinoma was admitted with hypercalcemia, suppressed PTH and hypophosphatemia. He was found to have metastatic anal squamous cell carcinoma to the liver. Further evaluation revealed elevated PTHrP and 1,25-dihydroxyvitamin D and low 25-hydroxyvitamin D. Over a 5-month course, the hypercalcemia responded poorly to bisphosphonates, transiently to prednisone, but showed marked improvement with chemotherapy. A review of English language publications in Pubmed and a reference search of retrieved articles revealed 29 cases of CRC causing PTHrP-mediated hypercalcemia. Most patients were middle-aged men (mean ± SD: 56.7 ± 13.4 years), with advanced metastatic cancer (85% with hepatic metastasis) and severe hypercalcemia (mean ± SD: 15.6 ± 1.9 mg/dL, 62% with Ca > 14). This condition is associated with high mortality (79%) and short survival (median 54.5 days, CI: 21 - 168). Despite being uncommon, HHM (PTHrP-mediated) should be considered in patients with metastatic CRC presenting with hypercalcemia. Clinicians should be aware that combined etiologies may be present, particularly in cases of resistant hypercalcemia. Treatment of the underlying malignancy is essential for calcium control.

Genetic and environmental interactions in obesity and type 2 diabetes.

Obesity and type 2 diabetes are increasing in prevalence, bringing with them considerable morbidity and mortality. The pathophysiology of each condition is quite complex and incompletely understood. Many hormone-like signaling agents that affect energy metabolism are released from adipocytes (eg, leptin) and from immune cells (eg, tumor necrosis factor-alpha). Type 2 diabetes and obesity are each characterized by the strong interaction of genetics and environment over time. A few single-gene defects have been found that lead to these conditions, but in most cases there is a polygenic contribution. In addition, several environmental factors such as lifestyle, social influences, and fetal surroundings may lead to development of these health problems. Genetic and environmental factors associated with these disorders are explored.