The safety and efficacy of dipeptidyl peptidase-4 (DPP4) inhibitors as monotherapy or in combination with other oral antidiabetic agents or basal insulin are well established. DPP4 inhibitors stimulate glucose-dependent insulin secretion and inhibit glucagon production. As monotherapy, they reduce the hemoglobin A1c level by about 0.6–0.8%. The addition of a DPP4 inhibitor to basal insulin is an attractive option, because they lower both postprandial and fasting plasma glucose concentrations without increasing the risk of hypoglycemia or weight gain. The present review summarizes the extensive evidence on the combination therapy of DPP4 inhibitors and insulin-based regimens in patients with type 2 diabetes. We focus our discussion on challenging clinical scenarios including patients with chronic renal impairment, elderly persons and hospitalized patients. The evidence indicates that these drugs are highly effective and safe in the elderly and in the presence of mild, moderate and severe renal failure improving glycemic control with low risk of hypoglycemia. In addition, several randomized-controlled trials have shown that the use of DPP4 inhibitors in combination with basal insulin represents an alternative to the basal-bolus insulin regimen in hospitalized patients with type 2 diabetes.
Hyperglycemia and elevated free fatty acids (FFA) are implicated in the development of endothelial dysfunction. Infusion of soy-bean oil-based lipid emulsion (Intralipid®) increases FFA levels and results in elevation of blood pressure (BP) and endothelial dysfunction in obese healthy subjects. The effects of combined hyperglycemia and high FFA on BP, endothelial function and carbohydrate metabolism are not known. Twelve obese healthy subjects received four random, 8-h IV infusions of saline, Intralipid 40 mL/h, Dextrose 10% 40 mL/h, or combined Intralipid and dextrose. Plasma levels of FFA increased by 1.03±0.34 mmol/L (p=0.009) after Intralipid, but FFAs remained unchanged during saline, dextrose, and combined Intralipid and dextrose infusion. Plasma glucose and insulin concentrations significantly increased after dextrose and combined Intralipid and dextrose (all, p<0.05) and were not different from baseline during saline and lipid infusion. Intralipid increased systolic BP by 12±9 mmHg (p<0.001) and diastolic BP by 5±6 mmHg (p=0.022), and decreased flow-mediated dilatation (FMD) from baseline by 3.2%±1.4% (p<0.001). Saline and dextrose infusion had neutral effects on BP and FMD. The co-administration of lipid and dextrose decreased FMD by 2.4%±2.1% (p=0.002) from baseline, but did not significantly increase systolic or diastolic BP. Short-term Intralipid infusion significantly increased FFA and BP; in contrast, FFA and BP were unchanged during combined infusion of Intralipid and dextrose. Combined Intralipid and dextrose infusion resulted in endothelial dysfunction similar to Intralipid alone.
Aims: There is a high prevalence of dental loss among patients with diabetes. Understanding the factors that impact dental loss in this population will aid with developing new strategies for its prevention. Methods Using a cross-sectional study design, patients with diabetes presenting for routine clinic visit were evaluated with an investigator-administered questionnaire. Data were collected on demographics, dental history, duration, control and complications of diabetes.
Results: Among 202 subjects, 100 were female, mean age: 58.9 ± 13.2 years, duration of diabetes: 15.8 ± 11.0 years, and hemoglobin A1c: 7.7 ± 1.6%. Thirty-one patients (15.3%) had lost all their teeth and only 13 patients (6.4%) had all 32 of their natural teeth. Using multiple linear regression, older age (β = −0.146; 95% CI: −0.062 to −0.230), not flossing (β = −3.462; 95% CI: −1.107 to −5.817), and presence of diabetic retinopathy (β = −4.271; 95% CI: −1.307 to −7.236) were significant predictors of dental loss.
Conclusions: Dental loss is common in patients with diabetes and is associated with older age, diabetic retinopathy and not flossing. In order to reduce dental loss among patients with diabetes, regular flossing should be emphasized as an important component of dental care.
by
Baraka Floyd;
Prakash Chandra;
Stephanie Hall;
Christopher Phillips;
Ernest Alema-Mensah;
Gregory Strayhorn;
Elizabeth O. Ofili;
Guillermo Umpierrez
Background: Self-monitoring of blood glucose (SMBG) and continuous glucose monitoring (CGM) have been proven effective in improving hemoglobin A1c (HbA1c) and in reducing hypoglycemia in patients with type 1 diabetes mellitus (T1DM). It is not clear, however, if CGM provides further efficacy and safety benefits beyond SMBG in the management of T1DM.
Methods: MEDLINE (1966–November 2009), COCHRANE REGISTRY (all years), and EMBASE (1980–November 2009), and article bibliographies were searched for randomized controlled trials (RCTs) investigating the use of CGM in patients with T1DM, with clinical outcomes, including HbA1c and hypoglycemia and/or hyperglycemia.
Results: Fourteen RCTs met eligibility criteria [n = 1188 patients, 97.4% with T1DM, age 29.0 ± 14.3 years, diabetes duration 11.7 ± 7.0 years, and baseline HbA1c 8.3 ± 0.8% (mean ± standard deviation)]. Compared with SMBG, the use of CGM was associated with a greater reduction in HbA1c [-0.3% (confidence interval: 0.4, -0.2), p < .0001]. The number of hypoglycemic events was not significantly different between the CGM and SMBG groups (0.52 ± 0.52 versus 0.52 ± 0.63 events/day, p = .5), but duration of hypoglycemia was shorter for the CGM group (75 ± 39 versus 89 ± 19 min/day), with an incremental reduction of hypoglycemia duration of -15.2 min/day, p < .0001. Continuous glucose monitoring also resulted in a shorter duration of hyperglycemia than SMBG (172 ± 125 versus 217 ± 152 min/day, p = .04).
Conclusions: The use of CGM is associated with improvement in metabolic control in T1DM, with significant short- and long-term reductions in HbA1c and reduction in the duration of periods of hypoglycemia and hyperglycemia versus SMBG.
Background: The underlying mechanisms for increased osteopenia and fracture rates in patients with diabetes are not well understood, but may relate to chronic systemic inflammation. We assessed the effect of treating periodontal disease (POD), a cause of chronic inflammation, on inflammatory and bone turnover markers in patients with diabetes.
Materials and Methods: Using an investigator-administered questionnaire, we screened a cross-section of patients presenting for routine outpatient diabetes care. We recruited 22 subjects with POD. Inflammatory and bone turnover markers were measured at baseline and 3 months following POD treatment (scaling, root planing and subantimicrobial dose doxycycline).
Results: There were nonsignificant reductions in high-sensitivity C-reactive protein (6.34–5.52 mg/L, P = 0.626) and tumor necrosis factor-alpha (10.37–10.01 pg/mL, P = 0.617). There were nonsignificant increases in urinary C-terminal telopeptide (85.50–90.23 pg/mL, P = 0.684) and bone-specific alkaline phosphatase (7.45–8.79 pg/mL, P = 0.074). Patients with >90% adherence with doxycycline were 6.4 times more likely to experience reduction in tumor necrosis factor-alpha (P = 0.021) and 2.8 times more likely to experience reductions in high-sensitivity C-reactive protein (P = 0.133).
Conclusions: Treatment of POD in patients with diabetes resulted in nonsignificant lowering of inflammatory markers and nonsignificant increase in bone turnover markers. However, adherence to doxycycline therapy resulted in better treatment effects.
Significant data suggest that overt hyperglycemia, either observed with or without a prior diagnosis of diabetes, contributes to an increase in mortality and morbidity in hospitalized patients. In this regard, goal-directed insulin therapy has remained as the standard of care for achieving and maintaining glycemic control in hospitalized patients with critical and noncritical illness. As such, protocols to assist in management of hyperglycemia in the inpatient setting have become commonplace in hospital settings. Clearly, insulin is a known entity, has been in clinical use for almost a century, and is effective. However, there are limitations to its use. Based on the observed mechanisms of action and efficacy, there has been a great interest in using incretin-based therapy with glucagon-like peptide-1 (GLP-1) receptor agonists instead of, or complementary to, an insulin-based approach to improve glycemic control in hospitalized, severely ill diabetic patients. To provide an understanding of both sides of the argument, we provide a discussion of this topic as part of this two-part point-counterpoint narrative. In the point narrative preceding the counterpoint narrative below, Drs. Schwartz and DeFronzo provide an opinion that now is the time to consider GLP-1 receptor agonists as a logical consideration for inpatient glycemic control. In the counterpoint narrative provided below, Drs. Umpierrez and Korytkowski provide a defense of insulin in the inpatient setting as the unquestioned gold standard for glycemic management in hospitalized settings.
Objective: We aimed to determine risk factors associated with hypoglycemia during subcutaneous insulin therapy in non-critically ill patients with type 2 diabetes.
Methods: We conducted an analysis of three randomized control trials using basal/bolus regimen and regular sliding scale insulin (SSI) in patients with diabetes admitted to medical and surgical settings.
Results: We analyzed medical records of 261 general medicine and 211 noncardiac surgery patients treated with basal/bolus regimen with glargine/glulisine (n = 169), detemir/aspart (n = 67), neutral protamine Hagedorn/regular (n = 63), or with SSI (n = 173). The overall frequency of mild and severe hypoglycemia (<70 and <40 mg/dl) was 19% and 2%, respectively. During treatment, medical patients experienced a higher number of hypoglycemia than surgical patients (23% versus 13%; p = .005), but the rate of severe hypoglycemia was similar between groups (1.9% versus 1.9%; p = not significant). Increasing age, impaired kidney function (glomerular filtration rate < 60 ml/min), total daily insulin dose, and type of insulin regimen (basal/bolus versus SSI) during hospitalization were important contributors for hypoglycemia in both medical and surgical patients. Among these variables, increasing age and type of insulin regimen (basal/bolus versus SSI) were found to be independent predictors of hypoglycemic events.
Conclusions: Mild hypoglycemic events are common during subcutaneous insulin therapy in medical and surgical patients with type 2 diabetes. Increasing age, impaired renal function, daily insulin dose, and insulin regimen (basal/bolus versus SSI) are important predictors of hypoglycemia during insulin therapy in patients with type 2 diabetes mellitus.
Background
Inpatient hyperglycemia in adult patients with and without a history of diabetes is a predictor of poor clinical outcome. No previous studies; however, have examined the association of hyperglycemia and clinical outcome in children admitted to a community pediatric hospital.
Methods
Retrospective observational cohort of pediatric patients admitted to a community children's hospital, from January 2004 to August 2004. Medical records of 903 consecutive children admitted to critical and non-critical care areas were reviewed. Of them, 342 patients (38%) had no blood glucose measurements during the hospital stay. In the remaining patients, we determined the prevalence of hyperglycemia and examined the association of hyperglycemia and clinical outcome.
Results
A total of 406 patients (75%) had an admission blood glucose ≤ 120 mg/dl [(mean 98 ± 1 mg/dl (± SEM)], 103 children (19%) had an admission blood glucose level between 121–179 mg/dl (mean 143 ± 2 mg/dl), and 32 patients (5.9%) had a blood glucose level ≥ 180 mg/dl (mean 260 ± 18 mg/dl). Seventeen patients (13%) had a known history of diabetes prior to admission. Children with hyperglycemia were more likely to be admitted to the ICU (p<0.001) and had a longer length of ICU stay (p<0.001), but admission hyperglycemia was not associated with longer hospital stay or higher hospital mortality.
Summary
Hyperglycemia is present in one-fourth of children admitted to the hospital, most of them without a history of diabetes prior to admission. Hyperglycemia was associated with a greater need for ICU care and longer ICU stay but not with increased in-hospital mortality.