Diabetic ketoacidosis (DKA) is a rare yet potentially fatal hyperglycemic crisis that can occur in patients with both type 1 and 2 diabetes mellitus. Due to its increasing incidence and economic impact related to the treatment and associated morbidity, effective management and prevention is key. Elements of management include making the appropriate diagnosis using current laboratory tools and clinical criteria and coordinating fluid resuscitation, insulin therapy, and electrolyte replacement through feedback obtained from timely patient monitoring and knowledge of resolution criteria. In addition, awareness of special populations such as patients with renal disease presenting with DKA is important. During the DKA therapy, complications may arise and appropriate strategies to prevent these complications are required. DKA prevention strategies including patient and provider education are important. This review aims to provide a brief overview of DKA from its pathophysiology to clinical presentation with in depth focus on up-to-date therapeutic management.

Hyperglycemia is a frequent complication of enteral and parenteral nutrition in hospitalized patients. Extensive evidence from observational studies indicates that the development of hyperglycemia during parenteral and enteral nutrition is associated with an increased risk of death and infectious complications. There are no specific guidelines recommending glycemic targets and effective strategies for the management of hyperglycemia during specialized nutritional support. Managing hyperglycemia in these patients should include optimization of carbohydrate content and administration of intravenous or subcutaneous insulin therapy. The administration of continuous insulin infusion and insulin addition to nutrition bag are efficient approaches to control hyperglycemia during parenteral nutrition. Subcutaneous administration of long-acting insulin with scheduled or corrective doses of short-acting insulin is superior to the sliding scale insulin strategy in patients receiving enteral feedings. Randomized controlled studies are needed to evaluate safe and effective therapeutic strategies for the management of hyperglycemia in patients receiving nutritional support.

Na(+)-K(+)-Cl(-) cotransporter (NKCC) activity in quiescent skeletal muscle is modest. However, ex vivo stimulation of muscle for as little as 18 contractions (1 min, 0.3 Hz) dramatically increased the activity of the cotransporter, measured as the bumetanide-sensitive (86)Rb influx, in both soleus and plantaris muscles. This activation of cotransporter activity remained relatively constant for up to 10-Hz stimulation for 1 min, falling off at higher frequencies (30-Hz stimulation for 1 min). Similarly, stimulation of skeletal muscle with adrenergic receptor agonists phenylephrine, isoproterenol, or epinephrine produced a dramatic stimulation of NKCC activity. It did not appear that stimulation of NKCC activity was a reflection of increased Na(+)-K(+)-ATPase activity because insulin treatment did not stimulate NKCC activity, despite insulin's well-known stimulation of Na(+)-K(+)-ATPase activity. Stimulation of NKCC activity could be blocked by pretreatment with inhibitors of mitogen-activated protein kinase (MAPK) kinase 1/2 (MEK1/2) activity, indicating that activation of the extracellular signal-regulated kinase 1/2 (ERK1/2) MAPKs may be required. These data indicate a regulated NKCC activity in skeletal muscle that may provide a significant pathway for potassium transport into skeletal muscle fibers.

etal muscle Na ϩ -K ϩ -2Cl Ϫ cotransporter (NKCC) activity provides a potential mechanism for regulated K ϩ uptake. ␤-Adrenergic receptor (␤-AR) activation stimulates skeletal muscle NKCC activity in a MAPK pathway-dependent manner. We examined potential G protein-coupled pathways for ␤-AR-stimulated NKCC activity. Inhibition of G s-coupled PKA blocked isoproterenol-stimulated NKCC activity in both the slow-twitch soleus muscle and the fast-twitch plantaris muscle. However, the PKA-activating agents cholera toxin, forskolin, and 8-bromo-cAMP (8-BrcAMP) were not sufficient to activate NKCC in the plantaris and partially stimulated NKCC activity in the soleus. Isoproterenol-stimulated NKCC activity in the soleus was abolished by pretreatment with pertussis toxin (PTX), indicating a G i-coupled mechanism. PTX did not affect the 8-BrcAMP-stimulated NKCC activity. PTX treatment also precluded the isoproterenol-mediated ERK1/2 MAPK phosphorylation in the soleus, consistent with NKCC's MAPK dependency. Inhibition of isoproterenolstimulated ERK activity by PTX treatment was associated with an increase in Akt activation and phosphorylation of Raf-1 on the inhibitory residue Ser 259 . These results demonstrate a novel, muscle phenotype-dependent mechanism for ␤-AR-mediated NKCC activation that involves both G s and G i protein-coupled mechanisms. potassium; mitogen-activated protein kinases; protein kinase A; pertussis toxin; Raf-1 SKELETAL MUSCLE IS WELL RECOGNIZED for its contribution to the regulation of plasma K ϩ concentration via insulin-, catecholamine-, and contraction-regulated Na ϩ -K

Background Blueberries are dietary sources of polyphenols, specifically anthocyanins. Anthocyanins have been identified as having a strong association with type 2 diabetes risk reduction; however, to date few human clinical trials have evaluated the potential beneficial health effects of blueberries in populations with type 2 diabetes. Objectives We investigated the effects of blueberry consumption for 8 wk on cardiometabolic parameters in men with type 2 diabetes. Methods In a double-blind, parallel-arm, randomized controlled trial, 52 men who are US veterans [mean baseline characteristics: age, 67 y (range: 51–75 y); weight, 102 kg (range: 80–130 kg); BMI (in kg/m2), 34 (range: 26–45)] were randomly assigned to 1 of 2 intervention groups. The interventions were either 22 g freeze-dried blueberries or 22 g placebo. The study participants were asked to consume 11 g freeze-dried blueberries or placebo with each of their morning and evening meals along with their typical diet. Results Mean ± SE hemoglobin A1c (7.1% ± 0.1% compared with 7.5% ± 0.2%; P = 0.03), fructosamine (275.5 ± 4.1 compared with 292.4 ± 7.9 µmol/L; P = 0.04), triglycerides (179.6 ± 10.1 compared with 199.6 ± 19.9 mg/dL; P = 0.03), aspartate transaminase (23.2 ± 1.4 compared with 30.5 ± 2.7 units/L; P = 0.02), and alanine transaminase (35.6 ± 1.5 compared with 48.3 ± 2.9 units/L; P = 0.0003) were significantly lower for those consuming blueberries for 8 wk than for those consuming the placebo. Fasting plasma glucose concentrations; serum insulin, total cholesterol, LDL-cholesterol, HDL-cholesterol, and C-reactive protein concentrations; blood pressure; and body weight were not significantly different after 8 wk consumption of blueberries compared with the placebo. Conclusions Consumption of 22 g freeze-dried blueberries for 8 wk may beneficially affect cardiometabolic health parameters in men with type 2 diabetes. This trial was registered at clinicaltrials.gov as NCT02972996.

We compared the effects of high and low oral and intravenous (iv) fat load on blood pressure (BP), endothelial function, autonomic nervous system, and oxidative stress in obese healthy subjects. Thirteen obese subjects randomly received five 8-h infusions of iv saline, 20 (32 g, low iv fat) or 40 ml/h intralipid (64 g, high iv fat), and oral fat load at 32 (low oral) or 64 g (high oral). Systolic BP increased by 14 ± 10 ( P = 0.007) and 12 ± 9 mmHg ( P = 0.007) after low and high iv lipid infusions and by 13 ± 17 ( P = 0.045) and 11 ± 11 mmHg ( P = 0.040) after low and high oral fat loads, respectively. The baseline flow-mediated dilation was 9.4%, and it decreased by 3.8 ± 2.1 ( P = 0.002) and 4.1 ± 3.1% ( P < 0.001) after low and high iv lipid infusion and by 3.8 ± 1.8 ( P = 0.002) and 5.0 ± 2.5% ( P < 0.001) after low and high oral fat load, respectively. Oral and iv fat load stimulated oxidative stress, increased heart rate, and decreased R-R interval variability. Acute iv fat load decreased blood glucose by 6–10 mg/dl ( P < 0.05) without changes in insulin concentration, whereas oral fat increased plasma insulin by 3.7–4.0 μU/ml ( P < 0.01) without glycemic variations. Intravenous saline and both oral and iv fat load reduced leptin concentration from baseline ( P < 0.01). In conclusion, acute fat load administered orally or intravenously significantly increased blood pressure, altered endothelial function, and activated sympathetic nervous system by mechanisms not likely depending on changes in leptin, glucose, and insulin levels in obese healthy subjects. Thus, fat load, independent of its source, has deleterious hemodynamic effects in obese subjects.

Several guidelines and position statements are published to help clinicians manage hypertension in patients with diabetes. Although there is an unequivocal call to treat hypertension in diabetes, professional organizations and experts have differing opinions regarding the most optimal blood pressure targets and treatments to lower vascular risks in the diabetes population. The objective of this article is to summarize the most recent hypertension management guidelines with particular attention to the origins and evidence behind these recommendations.

Recent studies have demonstrated that p44/42MAPK extracellular signal؊regulated kinase (ERK)1 and -2؊dependent Na ؉ -K ؉ -2Cl ؊ co-transporter (NKCC) activity may contribute to total potassium uptake by skeletal muscle. To study the precise mechanisms regulating NKCC activity, rat soleus and plantaris muscles were stimulated ex vivo by insulin or isoproterenol (ISO). Both hormones stimulated total uptake of the potassium congener 86 Rb by 25-70%. However, only ISO stimulated the NKCC-mediated 86 Rb uptake. Insulin inhibited the ISO-stimulated NKCC activity, and this counteraction was sensitive to the p38 mitogen-activated protein kinase (MAPK) inhibitor SB203580 in the predominantly slow-twitch soleus muscle. Pretreatment of the soleus muscle with the phosphatidylinositol (PI) 3-kinase inhibitors wortmannin and LY294002 or with SB203580 uncovered an insulin-stimulated NKCC activity and also increased the insulin-stimulated phosphorylation of ERK. In the predominantly fast-twitch plantaris muscle, insulin-stimulated NKCC activity became apparent only after inhibition of PI 3-kinase activity, accompanied by an increase in ERK phosphorylation. PI 3-kinase inhibitors also abolished insulin-stimulated p38 MAPK phosphorylation in the plantaris muscle and Akt phosphorylation in both muscles. These data demonstrated that insulin inhibits NKCC-mediated transport in skeletal muscle through PI 3-kinase؊sensitive and SB203580-sensitive mechanisms. Furthermore, differential activation of signaling cascade elements after hormonal stimulation may contribute to fiber-type specificity in the control of potassium transport by skeletal muscle. Diabetes 51:615-623, 2002