Insulin Secretion Predicts the Response to Antidiabetic Therapy in Patients With New-onset Diabetes.

CONTEXT: The results of the present study demonstrate that beta cell function in newly diagnosed T2DM patients is the key predictor of response to glucose lowering medications and provides a practical tool (C-Pep120 /C-Pep0) to guide the choice of glucose lowering agent. OBJECTIVE: This work aims to identify predictors for individualization of antidiabetic therapy in patients with new-onset type 2 diabetes mellitus (T2DM). METHODS: A total of 261 drug-naive participants in the Efficacy and Durability of Initial Combination Therapy for Type 2 Diabetes (EDICT) study, with new-onset diabetes, were randomly assigned in a single-center study to receive 1) metformin followed by glipizide and then insulin glargine on failure to achieve glycated hemoglobin A1c (HbA1c) less than 6.5%, or 2) initial triple therapy with metformin/pioglitazone/exenatide. Each patient received a 75-g oral glucose tolerance test (OGTT) prior to start of therapy. Factors that predicted response to therapy were identified using the area under the receiver operating characteristic curve method. RESULTS: Thirty-nine patients started and maintained the treatment goal (HbA1c < 6.5%) on metformin only, and did not require intensification of antihyperglycemic therapy; 54 patients required addition of glipizide to metformin; and 47 patients required insulin addition to metformin plus glipizide for glucose control. The plasma C-peptide concentration (C-Pep)120/C-Pep0 ratio during the OGTT was the strongest predictor of response to therapy. Patients with a ratio less than 1.78 were more likely to require insulin for glucose control, whereas patients with a ratio greater than 2.65 were more likely to achieve glucose control with metformin monotherapy. In patients started on initial triple therapy, the HbA1c decreased independently of the C-Pep120/C-Pep0 ratio. CONCLUSION: The increase in C-Pep above fasting following glucose load predicts the response to antihyperglycemic therapy in patients with new-onset diabetes. C-Pep120/C-Pep0 provides a useful tool for the individualization of antihyperglycemic therapy in patients with new-onset T2DM.

Effects of different metabolic states and surgical models on glucose metabolism and secretion of ileal L-cell peptides: results from the HIPER-1 study.

AIM: To compare the impact of four surgical procedures (mini-gastric bypass, sleeve gastrectomy, ileal transposition and transit bipartition) vs medical management on gut peptide secretion, ß-cell function and resolution of hyperglycaemia in people with type 2 diabetes. RESEARCH DESIGN AND METHODS: A mixed-meal tolerance test was administered 6-24 months after each surgical procedure (mini-gastric bypass, sleeve gastrectomy, ileal transposition and transit bipartition; n=30 in each group) and the results were compared with those obtained in matched lean (n=30) and obese (n=30) people with type 2 diabetes undergoing medical management. RESULTS: Participants in the mini-gastric bypass and ileal transposition groups had a greater increase in plasma glucose concentration after the mixed-meal tolerance test than those in the sleeve gastrectomy and transit bipartition groups. Participants in the mini-gastric bypass group exhibited the greatest increase in the incremental area under the curve of plasma glucose concentration above baseline (P<0.0001). Insulin sensitivity was similar across surgical groups, and statistically greater in participants in the surgical groups than in obese participants in the non-surgical group (P<0.0001). ß-cell responsiveness to glucose was greater in participants in the sleeve gastrectomy and transit bipartition groups than in the mini-gastric bypass and ileal transposition groups (P<0.001) despite a smaller incremental increase above baseline in the area under the plasma glucagon-like peptide-1 concentration curve relative to ileal transposition. Postoperative ß-cell function was the strongest predictor of hyperglycaemia resolution. CONCLUSIONS: The present study showed that the level of ß-cell function after bariatric surgery is the strongest predictor of hyperglycaemia resolution. The study also demonstrates a disconnect between postprandial GLP-1 levels and ß-cell function among the studied surgical procedures.

Validity of screening tools for dementia and mild cognitive impairment among the elderly in primary health care: a systematic review.

OBJECTIVES: This systematic review aims to provide updated and comprehensive evidence on the validity and feasibility of screening tools for mild cognitive impairment (MCI) and dementia among the elderly at primary healthcare level. STUDY DESIGN: A review of articles was performed. METHODS: A search strategy was used by using electronic bibliographic databases including PubMed, Embase and CENTRAL for published studies and reference list of published studies. The articles were exported to a bibliographic database for further screening process. Two reviewers worked independently to screen results and extract data from the included studies. Any discrepancies were resolved and confirmed by the consensus of all authors. RESULTS: There were three screening approaches for detecting MCI and dementia - screening by a healthcare provider, screening by a self-administered questionnaire and caretaker informant screening. Montreal Cognitive Assessment (MoCA) was the most common and preferable tool for MCI screening (sensitivity [Sn]: 81-97%; specificity [Sp]: 60-86%), whereas Addenbrooke's Cognitive Examination (ACE) was the preferable tool for dementia screening (Sn: 79-100%; Sp: 86%). CONCLUSION: This systematic review found that there are three screening approaches for detecting early dementia and MCI at primary health care. ACE and MoCA are recommended tools for screening of dementia and MCI, respectively.

Revitalization of pioglitazone: the optimum agent to be combined with a sodium-glucose co-transporter-2 inhibitor.

The recently completed EMPA-REG study showed that empagliflozin significantly decreased the major adverse cardiac events (MACE) endpoint, which comprised cardiovascular death, non-fatal myocardial infarction (MI) and stroke, in patients with high-risk type 2 diabetes (T2DM), primarily through a reduction in cardiovascular death, without a significant decrease in either MI or stroke. In the PROactive study, pioglitazone decreased the MACE endpoint by a similar degree to that observed in the EMPA-REG study, through a marked reduction in both recurrent MI and stroke and a modest reduction in cardiovascular death. These observations suggest that pioglitazone might be an ideal agent to combine with empagliflozin to further reduce cardiovascular events in patients with high-risk diabetes as empagliflozin also promotes salt/water loss and would be expected to offset any fluid retention associated with pioglitazone therapy. In the present paper, we provide an overview of the potential benefits of combined pioglitazone/empagliflozin therapy to prevent cardiovascular events in patients with T2DM.

Empagliflozin and linagliptin combination therapy for treatment of patients with type 2 diabetes mellitus.

INTRODUCTION: Many patients with type 2 diabetes mellitus (T2DM) fail to achieve the desired A1c goal because the antidiabetic medications used do not correct the underlying pathophysiologic abnormalities and monotherapy is not sufficiently potent to reduce the A1c to the 6.5 - 7.0% range. Insulin resistance and islet (beta and alpha) cell dysfunction are major pathophysiologic abnormalities in T2DM. We examine combination therapy with linagliptin plus empagliflozin as a therapeutic approach for the treatment of inadequately controlled T2DM patients. AREAS COVERED: A literature search of all human diabetes, metabolism and general medicine journals from year 2000 to the present was conducted. Glucagon like peptide-1 (GLP-1) deficiency/resistance contributes to islet cell dysfunction by impairing insulin secretion and increasing glucagon secretion. DPP-4 inhibitors (DPP4i) improve pancreatic islet function by augmenting glucose-dependent insulin secretion and decreasing elevated plasma glucagon levels. Linagliptin, a DPP-4 inhibitor, reduces HbA1c, is weight neutral, has an excellent safety profile and a low risk of hypoglycemia. The expression of sodium-glucose cotransporter-2 (SGLT2) in the proximal renal tubule is upregulated in T2DM, causing excess reabsorption of filtered glucose. The SGLT2 inhibitor (SGLT2i), empagliflozin, improves HbA1c by causing glucosuria and ameliorating glucotoxicity. It also decreases weight and blood pressure, and has a low risk of hypoglycemia. EXPERT OPINION: The once daily oral combination of linagliptin plus empagliflozin does not increase the risk of hypoglycemia and tolerability and discontinuation rates are similar to those with each as monotherapy. At HbA1c values below 8.5% linagliptin/empagliflozin treatment produces an additive effect, whereas above 8.5%, there is a less than additive reduction with combination therapy compared with the effect of each agent alone. Linagliptin/empagliflozin addition is a logical combination in patients with T2DM, especially those with an HbA1c < 8.5%.

Initial combination therapy with metformin, pioglitazone and exenatide is more effective than sequential add-on therapy in subjects with new-onset diabetes. Results from the Efficacy and Durability of Initial Combination Therapy for Type 2 Diabetes (EDICT): a randomized trial.

AIM: To test our hypothesis that initiating therapy with a combination of agents known to improve insulin secretion and insulin sensitivity in subjects with new-onset diabetes would produce greater, more durable reduction in glycated haemoglobin (HbA1c) levels, while avoiding hypoglycaemia and weight gain, compared with sequential addition of agents that lower plasma glucose but do not correct established pathophysiological abnormalities. METHODS: Drug-naïve, recently diagnosed subjects with type 2 diabetes mellitus (T2DM) were randomized in an open-fashion design in a single-centre study to metformin/pioglitazone/exenatide (triple therapy; n = 106) or an escalating dose of metformin followed by sequential addition of sulfonylurea and glargine insulin (conventional therapy; n = 115) to maintain HbA1c levels at <6.5% for 2 years. RESULTS: Participants receiving triple therapy experienced a significantly greater reduction in HbA1c level than those receiving conventional therapy (5.95 vs. 6.50%; p < 0.001). Despite lower HbA1c values, participants receiving triple therapy experienced a 7.5-fold lower rate of hypoglycaemia compared with participants receiving conventional therapy. Participants receiving triple therapy experienced a mean weight loss of 1.2 kg versus a mean weight gain of 4.1 kg (p < 0.01) in those receiving conventional therapy. CONCLUSION: The results of this exploratory study show that combination therapy with metformin/pioglitazone/exenatide in patients with newly diagnosed T2DM is more effective and results in fewer hypoglycaemic events than sequential add-on therapy with metformin, sulfonylurea and then basal insulin.

Satisfaction Of Patient In Undergraduate Periodontal Clinic At University Of Malaya

The aim of study was to evaluate the level of satisfaction of patients treated in the undergraduate Year 4and Year 5 of University of Malaya. The subjects were patients treated in the Year 4 periodontology clinic(Polyclinic B) (n=38) and Year 5 periodontology clinic (Polyclinic C) (n=30). Data was gathered using aquestionnaire which consisted of 4 components namely appointment facilities, infrastructure and basicfacilities, behaviour of students dental clinician, and quality and efficiency of treatment provided. Theresults showed that for appointment facilities the level of satisfaction was almost 80%; for infrastructureand basic facilities the satisfaction was more than 85%; for behavior of students dental clinician thelevel of satisfaction was more than 90% and for quality and efficiency of treatment provided the level ofsatisfaction was more than 60%. When all the components were compared between patients treated inPolyclinic B to patients treated in Polyclinic C, there was no statistically significant difference (p>0.05).In conclusion, the level of satisfaction of patients treated in the undergraduate Year 4 and Year 5periodontology clinic of University of Malaya is the same.Keywords: Facilities and infrastructure; patient satisfaction; periodontal treatment; pain; quality of thetreatment; undergraduate students

Lowering plasma glucose concentration by inhibiting renal sodium-glucose cotransport.

Maintaining normoglycaemia not only reduces the risk of diabetic microvascular complications but also corrects the metabolic abnormalities that contribute to the development and progression of hyperglycaemia, that is insulin resistance and beta-cell dysfunction. Progressive beta-cell failure, in addition to side effects associated with many current antidiabetic agents, for example hypoglycaemia and weight gain, presents major obstacles to the achievement of the recommended goal of glycaemic control in patients with type 2 diabetes mellitus (T2DM). Thus, novel effective therapies are needed for optimal glucose control in subjects with T2DM. Most recently, specific inhibitors of the renal sodium-glucose cotransporter 2 (SGLT2) have been developed to produce glucosuria and lower the plasma glucose concentration. Because of the iR unique mechanism of action, which is independent of insulin secretion and insulin action, these agents are effective in lowering the plasma glucose concentration in all stages of the disease and can be combined with all other antidiabetic agents. In this review, we will summarize the available data concerning the mechanism of action, efficacy and safety of this novel class of antidiabetic agents.

The effect of feto-maternal blood type incompatibility on development of gestational diabetes mellitus.

OBJECTIVE: To assess the relation between fetal and maternal blood type (ABO, Rh) incompatibility and development of gestational diabetes mellitus (GDM). MATERIALS AND METHODS: A total of 500 pregnant women underwent diagnostic test for GDM by a 100-g oral glucose tolerance test (OGTT) after an 8 to 12-h overnight fast participated in this study. OGTT was performed between the 24-28 weeks of gestation, but participants who were at high risk for GDM were tested after the first prenatal visit. In the postpartum period, maternal and infant blood types were determined. Presence of GDM was evaluated in terms of matched and unmatched fetal and maternal ABO and Rh blood types separately. RESULTS: GDM was detected in 235 participants. Unmatched ABO blood types between the mother-infant pairs were present in 44.7% (n=105) of GDM (+) and 35.8 % (n=95) of GDM (-) patients. Incompatible feto-maternal ABO blood type was positively correlated with development of GDM which was marginally significant. (p=0.045; R=1.2;95% CL; 1.004-1.48). However, Rh feto-maternal blood type incompatibility was not related with development of GDM. CONCLUSIONS: Feto-maternal ABO blood type incompatibility may be a weak risk factor for the development of GDM.

Relationship between patient satisfactions with diabetes care and treatment.

BACKGROUND: Measurement of treatment satisfaction in diabetes is important as it has been shown to be associated with positive outcomes, reduced disease cost and better health. AIM: The aim of this study was to assess the relationship between treatment satisfaction of diabetes patients and socioeconomic, clinical, medication adherence and health-related factors in Qatar. DESIGN: This is a cross-sectional study. SETTING: The survey was carried out in primary health care centers and hospitals from April 2010 to May 2011. SUBJECTS: Of a total of 3000 diabetic patients, 2582 patients gave their consent to take part in the study, with a response rate of 86.1%. MATERIALS AND METHODS: The Diabetes Treatment Satisfaction Questionnaire was used to measure the patient satisfaction. The modified Morisky Medication Adherence was used to measure medication taking behavior. A multivariate stepwise linear regression model was performed to identify factors independently associated with patients' satisfaction instrument. RESULTS: Of the studied patients, majority of the diabetes patients were Qataris (61.2%), married (86.1%), above secondary education (46.9%) and unemployed (28.6%). Diabetes patients who had professional jobs (3.97 ± 0.65; P = 0.009) and those who were staying alone had a significantly higher treatment satisfaction score (4.01 ± 0.64; P = 0.001) compared with the other patients. Patients who were taking tablets were significantly more satisfied with treatment (4.08 ± 0.60; P < 0.001). Diabetes patients of primary health care centers (3.96 vs. 3.80; P < 0.001) were more satisfied with treatment than patients visiting hospitals. Multivariate regression analysis revealed that age of the patient (P < 0.001), expatriates (P = 0.023), patients visiting hospitals (P < 0.001), treatment with insulin (P < 0.001) and any diabetes complications (P < 0.001) were significantly less satisfied with the treatment. CONCLUSION: The study findings revealed that patient satisfaction was positively associated with sociodemographic variables like high income, employment, married individuals and those with higher levels of education. We found a lower treatment satisfaction in patients with diabetes-related complications and insulin treatment.

Insulin vs GLP-1 analogues in poorly controlled Type 2 diabetic subjects on oral therapy: a meta-analysis.

AIM: To compare insulin and GLP-1 analogues therapy on glycemic control in poorly controlled Type 2 diabetes (T2DM) subjects failing on oral therapy. METHODS: The electronic database PubMed was systematically searched for randomized controlled trial (RCT) with duration >16 weeks comparing the addition of insulin therapy vs glucagon-like peptide (GLP-1) analogues in poorly controlled T2DM subjects on oral therapy. RESULTS: We identified 7 RCT with 2199 patients of whom 1119 were assigned to insulin therapy and 1080 received a GLP-1 analogue. Both insulin and GLP-1 analogues were effective in lowering glycated hemoglobin (HbA(1c)) with no statistically significant difference between the mean decreases in HbA(1c). However, insulin was more effective than GLP-1 analogues in lowering the fasting plasma glucose concentration, while GLP-1 agonists were more effective in lowering the postprandial glucose concentration. Insulin therapy was associated with weight gain while GLP-1 analogues consistently caused weight loss and the difference between the mean change in body weight between the two therapies was highly statistically significant. Despite a similar decrease in HbA(1c), the risk of hypoglycemia was 35% lower (p=0.001) with GLP-1 therapy compared to insulin. Compared to insulin, GLP-1 analogues caused a significant decrease in systolic blood pressure and were associated with greater rate of gastrointestinal adverse events. CONCLUSION/INTERPRETATION: In poorly controlled T2DM subjects on oral therapy, GLP-1 analogues and insulin are equally effective in lowering the HbA(1c). However, GLP-1 analogues have additional non-glycemic benefits and lower risk of hypoglycemia. Thus, GLP-1 analogues should be considered as a treatment option in this group of diabetic individuals.

Early metabolic defects in Arab subjects with strong family history of Type 2 diabetes.

AIMS AND OBJECTIVE: It is widely accepted that the genetic make-up of the subject plays a pivotal role in the development of insulin resistance and ß cell failure. The objective of this study was to examine whether the same or distinct genetic backgrounds contribute to the development of insulin resistance and ß cell failure. METHODS: We examined insulin sensitivity and ß cell function in lean normal glucose tolerance subjects from 3 multigeneration Arab families. Families 1 and 2 had strong history of Type 2 diabetes (T2DM), while no member of family 3 had T2DM. RESULTS: Subjects in family 1 manifested increased basal plasma free fatty acid (FFA) concentration and impaired suppression of plasma FFA during the OGTT compared to subjects in family 3. Subjects in family 2 had comparable fasting plasma FFA and suppression of plasma FFA during the OGTT to family 3. Both the absolute plasma glucose concentrations, and incremental area under the plasma glucose curve (ΔG0-120) during the OGTT were comparable in subjects of families 1 and 2, and were decreased in subjects of family 3. Whole body and muscle insulin sensitivity were comparable in subjects from families 2 and 3, and both were significantly decreased in subjects of family 1. Beta cell function was comparable in subjects of families 1 and 3 and was significantly decreased in subjects of family 2. CONCLUSION: These results demonstrate that distinct genetic background contributes to the development of insulin resistance and ß cell dysfunction in Arab individuals.

Chromatin occupancy of transcription factor 7-like 2 (TCF7L2) and its role in hepatic glucose metabolism.

AIMS/HYPOTHESIS: The mechanisms by which transcription factor 7-like 2 (TCF7L2) regulates the pathways that are important in the pathogenesis of type 2 diabetes are unknown. We therefore examined the role of TCF7L2 in hepatic glucose production (HGP) in vitro and characterised the whole-genome chromatin occupancy of TCF7L2 in hepatocytes. METHODS: We investigated the effect of TCF7L2 silencing and overexpression on HGP from gluconeogenic precursors and used chromatin-immunoprecipitation (ChIP) combined with massively parallel DNA sequencing (ChIP-Seq) to investigate the DNA binding patterns of TCF7L2 across the whole genome. RESULTS: Silencing of TCF7L2 induced a marked increase in basal HGP, which was accompanied by significant increases in the expression of the gluconeogenic genes Fbp1, Pck1 and G6pc. Overexpression of Tcf7l2 reversed this phenotype and significantly reduced HGP. TCF7L2 silencing did not affect the half-maximal inhibitory concentration of insulin or metformin, but HGP remained elevated in TCF7L2-silenced cells due to the increased baseline HGP. Using ChIP-Seq, we detected 2,119 binding events across the genome. Pathway analysis demonstrated that diabetes genes were significantly over-represented in the dataset. Our results indicate that TCF7L2 binds directly to multiple genes that are important in regulation of glucose metabolism in the liver, including Pck1, Fbp1, Irs1, Irs2, Akt2, Adipor1, Pdk4 and Cpt1a. CONCLUSIONS/INTERPRETATION: TCF7L2 is an important regulator of HGP in vitro and binds directly to genes that are important in pathways of glucose metabolism in the liver. These data highlight the possibility that TCF7L2 may affect fasting and postprandial hyperglycaemia in carriers of at-risk TCF7L2 genetic polymorphisms.

Mitochondrial reactive oxygen species generation in obese non-diabetic and type 2 diabetic participants.

AIMS/HYPOTHESIS: The aim of this study was to measure mitochondrial reactive oxygen species (ROS) production directly from skeletal muscle biopsies obtained from obese insulin-resistant non-diabetic and type 2 diabetic participants. METHODS: Ten lean healthy, ten obese non-diabetic and ten type 2 diabetic participants received a euglycaemic-hyperinsulinaemic clamp to measure whole body insulin sensitivity. Mitochondria were isolated from skeletal muscle biopsies, and mitochondrial ATP synthesis and hydrogen peroxide production were measured ex vivo under conditions that maximally stimulate ATP synthesis and ROS production using chemiluminescent and fluorescent techniques, respectively. RESULTS: Compared with lean controls, both obese non-diabetic and type 2 diabetic participants were resistant to insulin, and had a reduced rate of mitochondrial ATP production. Obese insulin-resistant participants had a decreased rate of mitochondrial ROS production, while ROS production rate in participants with type 2 diabetes was similar to that in lean healthy participants. In non-diabetic participants, the rate of ROS production was strongly correlated with the rate of ATP synthesis and the glucose disposal rate measured with the euglycaemic-hyperinsulinaemic clamp. The ROS/ATP ratio in obese insulin-resistant participants was similar to that in lean insulin-sensitive participants, while the ratio was significantly elevated in type 2 diabetes participants. CONCLUSIONS/INTERPRETATION: Since, in absolute terms, the maximal capacity for mitochondrial ROS production was not increased in either obese insulin-resistant participants or in type 2 diabetic participants, these results do not favour a role for increased mitochondrial ROS production in the pathogenesis of insulin resistance in human skeletal muscle. However, care should be taken in extrapolating these ex vivo observations to the in vivo situation.

Strong association between insulin resistance in liver and skeletal muscle in non-diabetic subjects.

OBJECTIVE: To examine the association between insulin resistance in skeletal muscle and liver in non-diabetic subjects. RESEARCH DESIGN AND METHODS: A total of 182 Mexican American subjects without Type 2 diabetes underwent an oral glucose tolerance test and euglycaemic-hyperinsulinaemic clamp performed with (3)[H]glucose. Insulin sensitivity in skeletal muscle was measured as the insulin-stimulated rate of total glucose disposal during the insulin clamp divided by steady-state plasma insulin concentration (TGD/SSPI). Hepatic insulin resistance was measured as the product of basal hepatic glucose production and fasting plasma insulin concentration (HGP x FPI). RESULTS: Hepatic insulin resistance was strongly correlated (r = 0.68, P < 0.0001) with skeletal muscle insulin resistance. Thirty-eight per cent of subjects had increased insulin resistance in both liver and skeletal muscle, while 39% were insulin sensitive in both skeletal muscle and liver. Twenty-three per cent of subjects were discordant for muscle and hepatic insulin resistance (P < 0.0001). Subjects with increased skeletal muscle insulin resistance had a higher 2-h plasma glucose concentration, greater incremental area under the plasma glucose concentration curve, lower fasting plasma insulin concentration and lower rate of basal hepatic glucose production compared with subjects with increased insulin resistance in liver. CONCLUSION: In non-diabetic subjects, insulin resistance in skeletal muscle is an important determinant of the fasting and 2-h plasma glucose concentrations and strongly correlates with hepatic insulin resistance.

Exhaled breath condensate pH and hydrogen peroxide as non-invasive markers for asthma.

OBJECTIVE: To estimate the predictive value of exhaled breath condensate (EBC) hydrogen peroxide (H2O2) concentration and pH as non-invasive markers in asthma. METHODS: Fifty patients with unstable, steroid naive atopic asthma were included in the study, 25 with intermittent asthma and 25 with persistent asthma. Asthma diagnosis was according to the National Heart Lung and Blood Institute guidelines for the diagnosis and management of asthma. Forced expiratory volume in one second (FEV1) was measured by computerized spirometry. The EBC H2O2 assay was carried out using the colorimetric assay. The study was conducted from January to December 2005 in the Asthma and Allergy Center, Tikrit, Iraq. RESULTS: The EBC H2O2 concentration was higher in the asthmatic group (0.91 micromol) as compared with the control (0.23 micromol). There was an inverse correlation between EBC H2O2 concentration and FEV1 predicted percent for asthmatic patients. The mean EBC pH was lower in the asthmatic than the control group. There was a positive correlation between EBC pH and FEV1 predicted percent for asthmatic patients. There was an inverse correlation between EBC H2O2 concentration and pH for all asthmatic patients, intermittent, and persistent asthmatic groups. CONCLUSION: Exhaled breath condensate hydrogen peroxide concentration and pH was a good non-invasive marker for asthma, whether it was with a persistent or intermittent course.

Reaction of sugars with 2-hydrazinopyridine, precursors for seco C-nucleosides of 1,2,4-triazolo[4,3-a]pyridine.

Reaction of 2-hydrazinopyridine (1) with D-xylose, D-galactose, D-glucose and D-fructose afforded the corresponding hydrazones mainly in the acyclic forms 2, 3, 6 and 11 with minor amounts of the cyclic structures. Oxidative cyclization of the hydrazones with bromine in methanol resulted in the formation of the 3-(polyhydroxyalkyl)-1,2,4-triazolo[4,3-a]pyridine derivatives 13-15 whose acetylation afforded the acetylated derivatives 16-18. Assignment of 1D and 2D NMR spectral data in addition to 15N NMR experiments led to complete characterization of the products.