Diabetic ketoacidosis

Diabetic ketoacidosis (DKA) is the most common acute hyperglycaemic emergency in people with diabetes mellitus. A diagnosis of DKA is confirmed when all of the three criteria are present — ‘D’, either elevated blood glucose levels or a family history of diabetes mellitus; ‘K’, the presence of high urinary or blood ketoacids; and ‘A’, a high anion gap metabolic acidosis. Early diagnosis and management are paramount to improve patient outcomes. The mainstays of treatment include restoration of circulating volume, insulin therapy, electrolyte replacement and treatment of any underlying precipitating event. Without optimal treatment, DKA remains a condition with appreciable, although largely preventable, morbidity and mortality. In this Primer, we discuss the epidemiology, pathogenesis, risk factors and diagnosis of DKA and provide practical recommendations for the management of DKA in adults and children

Diabetic Ketoacidosis and Hyperosmolar Hyperglycemic State

Acute hyperglycemic emergencies are a common cause of diabetes-related hospitalization. Diabetes ketoacidosis (DKA) is typically seen in patients with type 1 diabetes, and hyperosmolar hyperglycemic state (HHS) is typically seen in patients with type 2 diabetes. Presentation of DKA is acute with polyuria, polydipsia, and abdominal symptoms and characterized by hyperglycemia, ketonemia, and anion gap metabolic acidosis. Presentation of HHS is subacute with symptoms similar to DKA followed by altered mental status and extremely high blood glucose levels with high plasma osmolarity. The common precipitating causes of acute hyperglycemic emergencies include medication nonadherence, infections, and ischemic events. The key to treatment, for both DKA and HHS, is rehydration, insulin therapy, and electrolyte management. With proper treatment, mortality from acute hyperglycemic emergencies has been going down, but the morbidity is still very high

The relation of plasma homocysteine to radiographic knee osteoarthritis

SummaryObjectiveHomocysteine has been implicated in multiple diseases that involve changes in structural tissue. In vitro studies have found that it alters the structure of collagen cross-linking thus affecting stability and mineralization such as that occurring in bone tissue. In the present study we considered the possible relationship between plasma homocysteine levels and the development and progression of knee osteoarthritis (OA).MethodsThe study question was posed in 691 men and 966 women from the original and offspring cohorts of the Framingham Osteoarthritis Study. We divided individuals into three groups according to plasma homocysteine levels and compared their risk for the development of new and progression of existing OA. We adjusted for potential confounders including age, body mass index, weight change, and physical activity.ResultsIn the crude analysis, men in the middle homocysteine tertile were found to be at a greater risk than men in the lowest tertile for incident OA [odds ratios of 1.9 (1.1–3.5)]. This result persisted after adjusting for covariates [odds: 2.0, (1.1–3.8)]. No significant correlation was seen in women for the development of OA. In the evaluation of progression no significant trends were seen for both men and women.ConclusionsAlthough cellular and molecular studies of homocysteine-related pathophysiology suggest a possible correlation between plasma homocysteine levels and OA, the present clinical study did not conclusively demonstrate such an association. However, further research is needed to explore the role of homocysteine in specific aspects of OA etiopathogenesis

Comparison of Efficacy and Safety of Glargine and Detemir Insulin in the Management of Inpatient Hyperglycemia and Diabetes

OBJECTIVE: Glargine and detemir insulin are the two most commonly prescribed basal insulin analogues for the ambulatory and inpatient management of diabetes. The efficacy and safety of basal insulin analogues in the hospital setting has not been established. METHODS: This observational study compared differences in glycemic control and outcomes in non-intensive care unit patients with blood glucose (BG) >140 mg/dL who were treated with glargine or detemir, between January 1, 2012, and September 30, 2015, in two academic centers. RESULTS: Among 6,245 medical and surgical patients with hyperglycemia, 5,749 received one or more doses of glargine, and 496 patients received detemir during the hospital stay. There were no differences in the mean daily BG (glargine, 182 ± 46 mg/dL vs. detemir, 180 ± 44 mg/dL; P = .70). There were no differences in mortality, hospital complications, or re-admissions between groups (all, P>.05). After adjusting for potential confounders, there was no statistically significant difference in hypoglycemia rates between treatment groups. Patients treated with detemir required higher total daily basal insulin doses (0.27 ± 0.16 units/kg/day vs. 0.22 ± 0.15 units/kg/day; P<.001). Glargine-treated patients had statistically longer length of stay; however, this difference may not be clinically relevant (6.8 ± 7.4 days vs. 6.0 ± 6.3 days; P<.001). CONCLUSION: Our study indicates that treatment with glargine and detemir results in similar inpatient glycemic control in general medicine and surgery patients. Detemir treatment was associated with higher daily basal insulin dose and number of injections. A prospective randomized study is needed to confirm these findings. ABBREVIATIONS: BG = blood glucose BMI = body mass index CI = confidence interval eGFR = estimated glomerular filtration rate HbA1c = glycated hemoglobin ICD-9 = International Classification of Diseases, ninth revision ICU = intensive care unit IQR = interquartile range LOS = length-of-stay OR = odd ratio

Efficacy and Safety of Intensive Versus Nonintensive Supplemental Insulin With a Basal-Bolus Insulin Regimen in Hospitalized Patients With Type 2 Diabetes: A Randomized Clinical Study

OBJECTIVE: Administration of supplemental sliding scale insulin for correction of hyperglycemia in non-intensive care unit (ICU) patients with type 2 diabetes is frequently used with basal-bolus insulin regimens. In this noninferiority randomized controlled trial we tested whether glycemic control is similar with and without aggressive sliding scale insulin treatment before meals and bedtime in patients treated with basal-bolus insulin regimens. RESEARCH DESIGN AND METHODS: Patients with type 2 diabetes with admission blood glucose (BG) 140-400 mg/dL treated with basal-bolus insulin were randomized to intensive (correction for BG >140 mg/dL, n = 108) or to nonintensive (correction for BG >260 mg/dL, n = 107) administration of rapid-acting sliding scale insulin before meals and bedtime. The groups received the same amount of sliding scale insulin for BG >260 mg/dL. Primary outcome was difference in mean daily BG levels between the groups during hospitalization. RESULTS: Mean daily BG in the nonintensive group was noninferior to BG in the intensive group with equivalence margin of 18 mg/dL (intensive 172 ± 38 mg/dL vs. nonintensive 173 ± 43 mg/dL, P = 0.001 for noninferiority). There were no differences in the proportion of target BG readings of 70-180 mg/dL, 350 mg/dL (severe hyperglycemia) or total, basal, or prandial insulin doses. Significantly fewer subjects received sliding scale insulin in the nonintensive (n = 36 [34%]) compared with the intensive (n = 98 [91%] [P < 0.0001]) group with no differences in sliding scale insulin doses between the groups among those who received sliding scale insulin (intensive 7 ± 4 units/day vs. nonintensive 8 ± 4 units/day, P = 0.34). CONCLUSIONS: Among non-ICU patients with type 2 diabetes on optimal basal-bolus insulin regimen with moderate hyperglycemia (BG <260 mg/dL), a less intensive sliding scale insulin treatment did not significantly affect glycemic control

Comparison of the FreeStyle Libre Pro Flash Continuous Glucose Monitoring (CGM) System and Point-of-Care Capillary Glucose Testing in Hospitalized Patients With Type 2 Diabetes Treated With Basal-Bolus Insulin Regimen

OBJECTIVE: We compared the performance of the FreeStyle Libre Pro continuous glucose monitoring (CGM) and point-of-care capillary glucose testing (POC) among insulin-treated hospitalized patients with type 2 diabetes (T2D). RESEARCH DESIGN AND METHODS: This was a prospective study in adult patients with T2D admitted to general medicine and surgery wards. Patients were monitored with POC before meals and bedtime and with CGM during the hospital stay. Study end points included differences between POC and CGM in mean daily blood glucose (BG), hypoglycemia <70 and <54 mg/dL, and nocturnal hypoglycemia. We also calculated the mean absolute relative difference (MARD), ±15%/15 mg/dL, ±20%/20 mg/dL, and ±30%/30 mg/dL and error grid analysis between matched glucose pairs. RESULTS: Mean daily glucose was significantly higher by POC (188.9 ± 37.3 vs. 176.1 ± 46.9 mg/dL) with an estimated mean difference of 12.8 mg/dL (95% CI 8.3-17.2 mg/dL), and proportions of patients with glucose readings <70 mg/dL (14% vs. 56%) and <54 mg/dL (4.1% vs. 36%) detected by POC BG were significantly lower compared with CGM (all P < 0.001). Nocturnal and prolonged CGM hypoglycemia <54 mg/dL were 26% and 12%, respectively. The overall MARD was 14.8%, ranging between 11.4% and 16.7% for glucose values between 70 and 250 mg/dL and higher for 51-69 mg/dL (MARD 28.0%). The percentages of glucose readings within ±15%/15 mg/dL, ±20%/20 mg/dL, and ±30%/30 mg/dL were 62%, 76%, and 91%, respectively. Error grid analysis showed 98.8% of glucose pairs within zones A and B. CONCLUSIONS: Compared with POC, FreeStyle Libre CGM showed lower mean daily glucose and higher detection of hypoglycemic events, particularly nocturnal and prolonged hypoglycemia in hospitalized patients with T2D. CGM's accuracy was lower in the hypoglycemic range

Clinical Outcomes in Patients With Isolated or Combined Diabetic Ketoacidosis and Hyperosmolar Hyperglycemic State: A Retrospective, Hospital-Based Cohort Study

OBJECTIVE: Many patients with hyperglycemic crises present with combined features of diabetic ketoacidosis (DKA) and hyperosmolar hyperglycemic state (HHS). The implications of concomitant acidosis and hyperosmolality are not well known. We investigated hospital outcomes in patients with isolated or combined hyperglycemic crises. RESEARCH DESIGN AND METHODS: We analyzed admissions data listing DKA or HHS at two academic hospitals. We determined 1) the frequency distributions of HHS, DKA, and combined DKA-HHS (DKA criteria plus elevated effective osmolality); 2) the relationship of markers of severity of illness and clinical comorbidities with 30-day all-cause mortality; and 3) the relationship of hospital complications associated with insulin therapy (hypoglycemia and hypokalemia) with mortality. RESULTS: There were 1,211 patients who had a first admission with confirmed hyperglycemic crises criteria, 465 (38%) who had isolated DKA, 421 (35%) who had isolated HHS, and 325 (27%) who had combined features of DKA-HHS. After adjustment for age, sex, BMI, race, and Charlson Comorbidity Index score, subjects with combined DKA-HHS had higher in-hospital mortality compared with subjects with isolated hyperglycemic crises (adjusted odds ratio [aOR] 2.7; 95% CI 1.4, 4.9; P = 0.0019). In all groups, hypoglycemia (<40 mg/dL) during treatment was associated with a 4.8-fold increase in mortality (aOR 4.8; 95% CI 1.4, 16.8). Hypokalemia ≤3.5 mEq/L was frequent (55%). Severe hypokalemia (≤2.5 mEq/L) was associated with increased inpatient mortality (aOR 4.9; 95% CI 1.3, 18.8; P = 0.02). CONCLUSIONS: Combined DKA-HHS is associated with higher mortality compared with isolated DKA or HHS. Severe hypokalemia and severe hypoglycemia are associated with higher hospital mortality in patients with hyperglycemic crises

A Randomized Controlled Trial Comparing the Efficacy and Safety of IDegLira Versus Basal-Bolus in Patients With Poorly Controlled Type 2 Diabetes and Very High HbA1c ≥9-15%: DUAL HIGH Trial

OBJECTIVEIn participants with type 2 diabetes (T2D) and HbA1c >9.0-10.0%, guidelines recommend treatment with basal-bolus insulin. RESEARCH DESIGN AND METHODSThis randomized trial compared the efficacy and safety of insulin degludec and liraglutide (IDegLira) and basal-bolus among participants with high HbA1c ≥9.0-15.0%, previously treated with 2 or 3 oral agents and/or basal insulin, allocated (1:1) to basal-bolus (n = 73) or IDegLira (n = 72). The primary end point was noninferiority (0.4%) in HbA1c reduction between groups. RESULTSAmong 145 participants (HbA1c 10.8% ± 1.3), there was no statistically significant difference in HbA1c reduction (3.18% ± 2.29 vs. 3.00% ± 1.79, P = 0.65; estimated treatment difference (ETD) 0.18%, 95% CI -0.59, 0.94) between the IDegLira and basal-bolus groups. IDegLira resulted in significantly lower rates of hypoglycemia <70 mg/dL (26% vs. 48%, P = 0.008; odds ratio 0.39, 95% CI 0.19, 0.78), and less weight gain (1.24 ± 8.33 vs. 5.84 ± 6.18 kg, P = 0.001; ETD -4.60, 95% CI -7.33, -1.87). CONCLUSIONSIn participants with T2D and HbA1c ≥9.0-15.0%, IDegLira resulted in similar HbA1c reduction, less hypoglycemia, and less weight gain compared with the basal-bolus regimen