Faculty Bibliography

We present a case of recalcitrant post-surgical hypocalcemia caused by hypoparathyroidism further complicated by a chyle leak and treatment with octreotide. A 60-year-old man with 4 months of hoarseness, 10-poundweight loss, and right-sided neck mass presented with difficulty breathing for one week. Imaging showed a right laryngeal/ hypopharyngeal mass. Pathology results revealed an invasive squamous cell carcinoma. He underwent an extensive neck surgery, which included a total thyroidectomy with parathyroidectomy. Post-operative day 1, laboratory results revealed a corrected calcium of 7.6 mg/dL [8.0-10.2], magnesium of 1.2 mg/dL [ref 1.3-1.9], phosphorus of 5.3 mg/dL [2.7-4.5], parathyroid hormone of <6.3 pg/ mL, 25-hydroxyvitamin D level was 13.1 ng/mL. Patient denied symptoms of perioral numbness, tingling of extremites, or muscle cramping. Despite treatment with elemental calcium carbonate 12 grams daily, calcitriol 0.50 mcg daily, HCTZ 12.5 mg daily via PEG, his serum calcium levels remained low at 7.6 mg/dL. He required recurrent management with intravenous calcium gluconate. His severed throacic duct caused by a chyle leak was treated with octreotide 100 mg subcutaneously three times a day. Calcium carbonate was switched to calcium citrate 1900 mg three times a day to increase calcium absoprtion. The patient's chyle leak eventually resolved, octreotide was stopped, and his serum calcium further improved off of IV calcium. His calcium improved to 9.5 mg/dL and he was discharged with oral calcium citrate, calcitriol, and cholecalciferol. Extensive neck surgery caused hypoparathyroidism and a chyle leak, both contributing to hypocalcemia. Chyle contains calcium and fat soluble vitamin D. Octreotide decreases chyle flow and suppresses gastrointestinal hormones such as gastrin, decreasing the acid environment optimal for calcium carbonate absorption. The use of calcium citrate which is absorbed independently of gastric acidity, the resolution of the chyle leak, and the cessation of octreotide improved serum calcium levels. Post-surgical hypoparathyroidism can lead to hypocalcemia. This case is unique in that chyle leak and use of octreotide contributed to recalcitrant hypocalcemia

OBJECTIVE:Systemic inflammation contributes to cardiovascular disease in patients with type 2 diabetes, and elevated white blood cell (WBC) counts are an established risk factor. Our goal is to describe changes in WBCs and inflammatory markers after glycemic reductions in diabetes. RESEARCH DESIGN AND METHODS/METHODS:This study enrolled 63 subjects with poorly controlled diabetes, defined as hemoglobin A1c (HbA1c) ≥8% [64 mmol/mol]. Circulating granulocytes and mononuclear cells were separated by histopaque double-density protocol. Inflammatory markers from these isolated WBCs were assessed at baseline and after 3 months of medical management. RESULTS:After 3 months, significant glycemic reduction, defined as a decrease in HbA1c ≥ 1.5%, occurred in 42 subjects. Fasting plasma glucose decreased by 47% (165.6 mg/dL), and HbA1c decreased from 10.2 ± 1.8 to 6.8 ± 0.9. Glycemic reductions were associated with a 9.4% decrease in total WBC counts, 10.96% decrease in neutrophils, and 21.74% decrease in monocytes. The mRNA levels of inflammatory markers from granulocytes and mononuclear cells decreased, including receptor for advanced glycation endproducts; S100 calcium binding proteins A8, A9, A12; krüppel-like factor 5; and IL-1. Also, circulating levels of IL-1β and C-reactive protein decreased. Insulin dose was a mediator between HbA1c and both total WBC and neutrophil counts, but not changes in WBC inflammatory markers. In contrast, the 17 subjects without significant glycemic reductions showed no significant differences in their WBC counts and proteins of inflammatory genes. CONCLUSION/CONCLUSIONS:Significant glycemic reduction in subjects with poorly controlled diabetes led to reduced circulating WBC counts and inflammatory gene expression.

Identifying the earliest moment for intervention to avert progression to prediabetes and diabetes in high-risk individuals is a substantial challenge. As β-cell function is already compromised in prediabetes, attention should therefore be focused on identifying high-risk individuals earlier in the so-called pre-prediabetes stage. Biomarkers to monitor progression and identify the time point at which β-cell dysfunction occurs are therefore critically needed. Large-scale population studies have consistently shown that the 1-h plasma glucose (1-h PG) ≥ 155 mg/dl (8.6 mmol/l) during the oral glucose tolerance test detected incident type 2 diabetes and associated complications earlier than fasting plasma glucose or 2-h plasma glucose levels. An elevated 1-h PG level appears to be a better alternative to HbA1c [5.7-6.4% (37-47 mmol/mol)] or traditional glucose criteria for identifying high-risk individuals at a stage when ß-cell function is substantially more intact than in prediabetes. Diagnosing high-risk individuals earlier proffers the opportunity for potentially reducing progression to diabetes, development of microvascular complications and mortality, thereby advancing benefit beyond that which has been demonstrated in global diabetes prevention programs.

Identifying the earliest time point on the prediabetic continuum is critical to avoid progressive deterioration in beta-cell function. Progressively rising glucose levels even within the "normal range" occur considerably late in the evolution to diabetes thus presenting an important opportunity for earlier diagnosis, treatment, and possible reversal. An elevated 1 h postprandial glucose level, not detected by current diagnostic standards, may provide an opportunity for the early identification of those at risk. When the 1 h post-load glucose level is elevated, lifestyle intervention may have the greatest benefit for preserving beta-cell function and prevent further progression to prediabetes and diabetes. In view of the considerable consistent epidemiologic data in large disparate populations supporting the predictive capacity of the1 h post-load value for predicting progression to diabetes and mortality, the time is therefore ripe to evaluate this hypothesis in a large, prospective multicenter randomized trial with lifestyle intervention.

The number of individuals with prediabetes is expected to grow substantially and estimated to globally affect 482 million people by 2040. Therefore, effective methods for diagnosing prediabetes will be required to reduce the risk of progressing to diabetes and its complications. The current biomarkers, glycated hemoglobin (HbA1c), fructosamine, and glycated albumin have limitations including moderate sensitivity and specificity and are inaccurate in certain clinical conditions. Therefore, identification of additional biomarkers is being explored recognizing that any single biomarker will also likely have inherent limitations. Therefore, combining several biomarkers may more precisely identify those at high risk for developing prediabetes and subsequent progression to diabetes. This review describes recently identified biomarkers and their potential utility for addressing the burgeoning epidemic of dysglycemic disorders.