Alterations in Postprandial Hepatic Glycogen Metabolism in Type 2 Diabetes

Decreased skeletal muscle glucose disposal and increased endogenous glucose production (EGP) contribute to postprandial hyperglycemia in type 2 diabetes, but the contribution of hepatic glycogen metabolism remains uncertain. Hepatic glycogen metabolism and EGP were monitored in type 2 diabetic patients and nondiabetic volunteer control subjects (CON) after mixed meal ingestion and during hyperglycemic-hyperinsulinemic-somatostatin clamps applying 13C nuclear magnetic resonance spectroscopy (NMRS) and variable infusion dual-tracer technique. Hepatocellular lipid (HCL) content was quantified by 1H NMRS. Before dinner, hepatic glycogen was lower in type 2 diabetic patients (227 ± 6 vs. CON: 275 ± 10 mmol/l liver, P < 0.001). After meal ingestion, net synthetic rates were 0.76 ± 0.16 (type 2 diabetic patients) and 1.36 ± 0.15 mg · kg−1 · min−1 (CON, P < 0.02), resulting in peak concentrations of 283 ± 15 and 360 ± 11 mmol/l liver. Postprandial rates of EGP were ∼0.3 mg · kg−1 · min−1 (30–170 min; P < 0.05 vs. CON) higher in type 2 diabetic patients. Under clamp conditions, type 2 diabetic patients featured ∼54% lower (P < 0.03) net hepatic glycogen synthesis and ∼0.5 mg · kg−1 · min−1 higher (P < 0.02) EGP. Hepatic glucose storage negatively correlated with HCL content (R = −0.602, P < 0.05). Type 2 diabetic patients exhibit 1) reduction of postprandial hepatic glycogen synthesis, 2) temporarily impaired suppression of EGP, and 3) no normalization of these defects by controlled hyperglycemic hyperinsulinemia. Thus, impaired insulin sensitivity and/or chronic glucolipotoxicity in addition to the effects of an altered insulin-to-glucagon ratio or increased free fatty acids accounts for defective hepatic glycogen metabolism in type 2 diabetic patients

Type 2 diabetes care: Improvement by standardization at a diabetes rehabilitation clinic. An observational report.

BACKGROUND:Outcome of type 2 diabetes care depends on the acceptance of self-responsibility by informed patients, as treatment goals will otherwise be missed. AIMS AND METHODS:This pre/post-observational report describes the clinical outcome of type 2 diabetes care in patients with type 2 diabetes (N =930) admitted consecutively to a diabetes rehabilitation clinic (DRC) between June 2013, and June 2016, where they were exposed to standardized lifestyle modification with meals low in salt and rich in vegetables and fruits, totaling 1,200 to 1,600 kcal/d, and an add-on exercise load equivalent to 400-600 kcal/d. RESULTS:At admission, patients presented with multiple treatment modes, elevated HbA1c levels (7.6±1.5%, 60±16 mmol/mol), a high prevalence of co-morbidities dominated by obesity (79%), a low rate of influenza and pneumococcal immunization (<9%) and underuse of lipid-lowering drugs (-29%). Analysis of clinical and metabolic outcome after 3 weeks shows that simple standardization of and better adherence to treatment recommendations improved (p<0.0001) glucose (HbA1c -0.4±0.4%) and lipid metabolism (LDL/HDL ratio, -0.58±0.03), permitting a 39% reduction in insulin dosage, omission of insulin in 36/232 patients and omission of oral antidiabetic drugs (OADs) other than metformin and DPP4-inhibitors, while the use of GLP-1 analogs doubled to 5.2%. Improved outcome was independent of treatment strategy and more marked at initially high HbA1c at costs less than 25% of those encountered at a standard hospital. CONCLUSIONS:Our observations support the clinical notion that adherence to basic treatment recommendations is indispensable in type 2 diabetes care if metabolic and clinical treatment goals are to be met, and if inappropriate add-on over-medicalization with OADs and/or insulin is to be avoided. To this end, 'imprinting' patients at a DRC could be of considerable help

Bases moleculares del reconocimiento de antígenos

Aunque todos los organismos pertenecientes al reino animal poseen una serie de mecanismos inmunitarios que persiguen mantener su integridad y rechazar la invasión de material foráneo, solo los vertebrados cuentan con un sofisticado sistema de reconocimiento específico, capaz de discriminar entre las distintas formas que puede presentar dicho material, en especial los microorganismos. El tipo celular que permitió el surgimiento de un sistema inmune específico es el linfocito, presente en todos los vertebrados, desde los peces más primitivos hasta los mamíferos superiores. Su característica principal es la capacidad de reconocimiento selectivo de los antígenos, a través de proteínas de superficie celular especializadas para tal fin.UCR::Vicerrectoría de Investigación::Unidades de Investigación::Ciencias de la Salud::Instituto Clodomiro Picado (ICP

Baseline characteristics of T1D patients (N = 109) segregated for females and males.

<p>Baseline characteristics of T1D patients (N = 109) segregated for females and males.</p

Type 1 diabetes care: Improvement by standardization in a diabetes rehabilitation clinic. An observational report - Fig 2

<p>(a) Inverse correlation between HbA_1c values at admission and their relative changes in response to a 3-week stay at the DRC in type 1 diabetes patients (N = 109). <u>Insert</u>: ROC-curve from a binary logistic regression model predicting from baseline possible HbA_1c improvement (>6.0 relative %) in response to proper treatment. (b) Strategies of insulin treatment used by type 1 diabetes patients (N = 109) at admission and at discharge. Note the shift towards more elaborate treatment modes. BOT, Basal supported oral therapy; CIT, Conventional insulin therapy; IIT (± CSII), Intensified insulin therapy ± continuous subcutaneous insulin infusion, FIT (± CSII), Functional insulin (basis/bolus) therapy ± continuous subcutaneous insulin infusion.</p

Type 1 diabetes care: Improvement by standardization in a diabetes rehabilitation clinic. An observational report - Fig 1

<p>(a) Co-morbidities (N,%) in type 1 diabetes patients (N = 109). CHD, coronary heart disease; PAD, peripheral artery disease; HT, hypothyreoidism; COPD, chronic obstructive pulmonary disease, and (b) correlation of NDS (neuropathic deficit score) with duration of disease (ρ = 0.368, p<.01).</p