Glycemic Monitoring and Management in Advanced Chronic Kidney Disease.

Glucose and insulin metabolism in patients with diabetes are profoundly altered by advanced chronic kidney disease (CKD). Risk of hypoglycemia is increased by failure of kidney gluconeogenesis, impaired insulin clearance by the kidney, defective insulin degradation due to uremia, increased erythrocyte glucose uptake during hemodialysis, impaired counterregulatory hormone responses (cortisol, growth hormone), nutritional deprivation, and variability of exposure to oral antihyperglycemic agents and exogenous insulin. Patients with end-stage kidney disease frequently experience wide glycemic excursions, with common occurrences of both hypoglycemia and hyperglycemia. Assessment of glycemia by glycated hemoglobin (HbA1c) is hampered by a variety of CKD-associated conditions that can bias the measure either to the low or high range. Alternative glycemic biomarkers, such as glycated albumin or fructosamine, are not fully validated. Therefore, HbA1c remains the preferred glycemic biomarker despite its limitations. Based on observational data for associations with mortality and risks of hypoglycemia with intensive glycemic control regimens in advanced CKD, an HbA1c range of 7% to 8% appears to be the most favorable. Emerging data on the use of continuous glucose monitoring in this population suggest promise for more precise monitoring and treatment adjustments to permit fine-tuning of glycemic management in patients with diabetes and advanced CKD.

Changes in metformin use and other antihyperglycemic therapies after insulin initiation in patients with type 2 diabetes.

AIMS: When patients with type 2 diabetes initiate insulin, metformin should be continued while continuation of other antihyperglycemics has unclear benefit. We aimed to identify practice patterns in antihyperglycemic therapy during the insulin transition, and determine factors associated with metformin continuation. METHODS: We performed a retrospective analysis of the Look AHEAD (Action for Health in Diabetes) trial which randomized overweight/obese adults under ambulatory care for type 2 diabetes to an intensive lifestyle intervention or diabetes support and education. Among the 931 participants who initiated insulin over ten years, we described longitudinal changes in antihyperglycemic medications during the insulin transition, and performed multivariable logistic regression to estimate the association between patient characteristics and metformin continuation. RESULTS: Before insulin initiation, 81.0% of patients used multiple antihyperglycemics, the most common being metformin, sulfonylureas, and thiazolidinediones. After insulin initiation, metformin was continued in 80.3% of patients; other antihyperglycemics were continued less often, yet 58.0% of patients were treated with multiple non-insulin antihyperglycemics. Metformin continuation was inversely associated with age (fully adjusted (a) OR 0.60 per 10 years [0.42-0.86]), serum creatinine above safety thresholds (aOR 0.09 [0.02-0.36]), lower income (P = 0.025 for trend), taking more medications (aOR 0.92 per medication [0.86-0.98]), and initiating rapid, short, or premixed insulin (aOR 0.59 [0.39-0.89]). CONCLUSIONS: The vast majority of patients with type 2 diabetes continue metformin after insulin initiation, consistent with guidelines. Other antihyperglycemics are frequently continued along with insulin, and further research is needed to determine which, if any, patients may benefit from this.

Predictors of Insulin Initiation in Patients with Type 2 Diabetes: An Analysis of the Look AHEAD Randomized Trial.

BACKGROUND: The decision to initiate insulin in patients with type 2 diabetes is a challenging escalation of care that requires an individualized approach. However, the sociodemographic and clinical factors affecting insulin initiation are not well understood. OBJECTIVE: We sought to identify patient factors that were independent predictors of insulin initiation among participants in the Look AHEAD (Action for Health in Diabetes) clinical trial. DESIGN: Retrospective analysis of a randomized clinical trial. PARTICIPANTS: Beginning in 2001, Look AHEAD enrolled ambulatory U.S. adults with type 2 diabetes who were overweight or obese and had a primary healthcare provider. Participants were randomized (1:1) to an intensive lifestyle intervention, or diabetes support and education. This study examined 3913 participants across the two trial arms who were not using insulin at baseline. MAIN MEASURES: We used Cox proportional hazards models to estimate the association between participant characteristics and time to insulin initiation. We performed time-varying adjustment for HbA1c measured eight times over the 10-year study period, as well as for multiple clinical and socioeconomic factors. KEY RESULTS: A total of 1087 participants (27.8%) initiated insulin during a median follow-up of 8.0 years. Age was inversely associated with insulin initiation (adjusted hazard ratio [aHR] 0.88 per 10 years, P = 0.025). The risk of insulin initiation was greater with a higher number of diabetes complications (P < 0.001 for trend); chronic kidney disease and cardiovascular disease were independently associated with insulin initiation. There was a lower risk of insulin initiation in black (aHR 0.77, P = 0.008) and Hispanic participants (aHR 0.66, P < 0.001) relative to white participants. Socioeconomic factors were not associated with insulin initiation. CONCLUSIONS: Patient age, race/ethnicity, and diabetes complications may influence insulin initiation in type 2 diabetes, independent of glycemic control. Future work is needed to understand the drivers of racial differences in antihyperglycemic treatment, and to identify patients who benefit most from insulin.

A quadruply-asymmetric sigmoid to describe the insulin-glucose relationship during intravenous insulin infusion.

For hospitalized patients requiring intravenous insulin therapy, an objective is to quantify the intravenous insulin infusion rate (IR) across the domain of blood glucose (BG) values at a single timepoint. The algorithm parameters include low BG (70 mg/dL), critical high BG, target range BG limits, and maintenance rate (MR) of insulin infusion, which, after initialization, depends on rate of change of blood glucose, previous IR, and other inputs. The restraining rate (RR) is a function of fractional completeness of ascent of BG (FCABG) from BG 70 mg/dL to target. The correction rate (CR) is a function of fractional elevation of BG (FEBG), in comparison to elevation of a critical high BG, above target. IR = RR + CR. The proposed mathematical model describing a sigmoidal relationship between IR and BG may offer a safety advantage over the linear relationship currently employed in some intravenous glucose management systems.

Therapeutic effect of sitagliptin combined insulin in treatment of type 2 Diabetes / 中国医师杂志

Objective To explore the clinical effect of sitagliptin combined insulin compared to those patients whose sugars were not well controlled by insulin alone.Methods The eighty type 2 Diabetes patients whose BMI≥24 kg/m2 and used insulin alone were randomly divided into sitagliptin combined insulin group (40 cases) who were given sitagliptin 100mg/d allied with insulin,an insulin group (40 cases) who were given insulin alone.After 12 weeks,the change of body mass index (BMI),fasting plasma glucose (FPG),2 h postprandial blood glucose (2 h PBG),glycosylated hemoglobin (HbA1 c),β-cell function index(HOMA-β),insulin resistance index (HOMA-IR),insulin quantities,and hypoglycemia rates were observed in two groups.Results Compared with pretherapy,the levels of FPG,2 h BG,HbAlc,HOMA-IR,and hypoglycemia rates were significantly decreased (P ＜0.05) ; BMI was increased in insulin group,while was not increased in sitagliptin combined insulin group.After the treatment,the insulin quantities were decreased in the combined group while increased in the control group (P ＜ 0.05).Conclusions Sitagliptin combined insulin can effectively control glucose levels of type 2 diabetes patients,decrease the insulin quantities and the risk of hypoglycemia,and does not increase the weight.

Hyperinsulinemia euglycemia therapy for calcium channel blocker overdose: a case report.

We report the case of a patient with calcium channel blocker toxicity who was treated successfully with hyperinsulinemia euglycemia therapy, without prior use of vasopressors. The patient was a 60-year-old man with schizoaffective disorder who presented with severe hemodynamic compromise after an intentional overdose of 5,400 mg of extended-release diltiazem. He had been admitted to the hospital twice before for attempted suicide with diltiazem and nifedipine, respectively. During the previous admissions, conventional treatments were used, and complications included hemodynamic compromise, ischemic bowel requiring ileostomy, and a prolonged hospital stay. During the current admission, the patient's clinical condition failed to improve after treatment with charcoal, fluid resuscitation, calcium, and glucagon. Eight hours after admission, hyperinsulinemia euglycemia therapy was initiated; 3 hours later, the patient's hemodynamic status showed sustained improvement. His bradycardia and hypotension resolved without cardiac pacing or vasopressors. Hyperinsulinemia euglycemia therapy is a potentially life-saving treatment for calcium channel blocker toxicity. We suggest that such therapy should be considered early, in conjunction with conventional therapy, for the treatment of calcium channel blocker overdose in patients not responding to initial treatment.

The roles and administration methods of insulin in the early treatment of acute brain injury / 中国医师杂志

Objective To explore the roles of insulin in the early treatment of acute brain injury and its administration methods.Methods 253 patients were randomly divided into the intensive insulin therapy group and the conventional therapy group.Infection rates,the short-term effect (APACHE Ⅱ assessment),and long-term efficacy (GOS prognosis) was compared between two groups.Results The results of the strengthen treatment group in the rate of infection (25.95％ vs 39.34％,x2 =5.17,P ＜0.05),the short-term effect (11.33 ± 7.66 vs 16.49 ± 14.97,u =3.42,P ＜ 0.05) and the long-term efficacy (40.46％,55.73％,3.82％ vs 25.41％,68.85％,5.74％,x2 =7.62,P ＜0.05) were significantly better than the conventional therapy group with the statistically significant differences (P ＜ 0.05).Conclusions The hypoglycemic effect,neuroprotective effect,regulatory role,and nutrition role of insulin occurred in the early treatment of acute brain injury.After acute brain injury,patients with hyperglycemia should be treated early with an enough volume,continuous,and uniform insulin.