Juan José Gagliardino

Multifaceted Determinants for Achieving Glycemic Control: The International Diabetes Management Practice Study (IDMPS)

OBJECTIVE—The International Diabetes Mellitus Practice Study is a 5-year survey documenting changes in diabetes treatment practice in developing regions. RESEARCH DESIGN AND METHODS—Logistic regression analysis was used to identify factors for achieving A1C <7% in 11,799 patients (1,898 type 1 diabetic and 9,901 type 2 diabetic) recruited by 937 physicians from 17 countries in Eastern Europe (n = 3,519), Asia (n = 5,888), Latin America (n = 2,116), and Africa (n = 276). RESULTS—Twenty-two percent of type 1 diabetic and 36% of type 2 diabetic patients never had A1C measurements. In those with values for A1C, blood pressure, and LDL cholesterol, 7.5% of type 1 diabetic (n = 696) and 3.6% of type 2 diabetic (n = 3,896) patients attained all three recommended targets (blood pressure <130/80 mmHg, LDL cholesterol <100 mg/dl, and A1C <7%). Self-monitoring of blood glucose was the only predictor for achieving the A1C goal in type 1 diabetes (odds ratios: Asia 2.24, Latin America 3.55, and Eastern Europe 2.42). In type 2 diabetes, short disease duration (Asia 0.97, Latin America 0.97, and Eastern Europe 0.82) and treatment with few oral glucose–lowering drugs (Asia 0.64, Latin America 0.76, and Eastern Europe 0.62) were predictors. Other region-specific factors included lack of microvascular complications and old age in Latin America and Asia; health insurance coverage and specialist care in Latin America; lack of obesity and self-adjustment of insulin dosages in Asia; and training by a diabetes educator, self-monitoring of blood glucose in patients who self-adjusted insulin, and lack of macrovascular complications in Eastern Europe. CONCLUSIONS—In developing countries, factors pertinent to patients, doctors, and health care systems all impact on glycemic control.

Real-world factors affecting adherence to insulin therapy in patients with Type 1 or Type 2 diabetes mellitus: a systematic review

To identify real‐world factors affecting adherence to insulin therapy in patients with Type 1 or Type 2 diabetes mellitus.

Long-term administration of a sucrose-rich diet to normal rats: Relationship between metabolic and hormonal profiles and morphological changes in the endocrine pancreas

The aim of the present investigation was to study normal rats fed a sucrose-rich diet (SRD) for a prolonged period (up to 30 weeks) (1) to obtain additional data on the hormonal and metabolic patterns induced by this treatment and (2) to provide information on changes taking place in the pancreatic islet cell populations. We found that long-term feeding with a SRD resulted in a steady state of hypertriglyceridemia and hyperglycemia in which insulin levels remained unchanged and unable to compensate for the increased demands of the developing metabolic changes. The endocrine pancreas showed a significant increase of both islet number and B-cell area, as well as changes in the profile of islet cell distribution. However, these changes were not accompanied by an increase in the pancreatic content of immunoreactive insulin (IRI). It may therefore be postulated that the newly emerged B-cell mass has some sort of derangement with the increased insulin demand resulting from insulin resistance induced by the long-term SRD feeding. Thus, feeding a SRD to normal rats may prove to be an attractive animal model for studying the role of environmental nutritional factors in the unsettled issue of the relationship between insulin resistance and relative insulin deficiency. The model might provide key information for understanding the pathophysiology of human diseases such as type II diabetes, dyslipidemia, and a number of entities included in so-called syndrome X.

Circadian Variation of the Blood Glucose, Plasma Insulin and Human Growth Hormone Levels in Response to an Oral Glucose Load in Normal Subjects

Circadian variations in blood glucose, plasma insulin and human growth hormone response were studied in six healthy males who received 100 gm. oral glucose loads at 6 a.m., noon, 6 p.m., and midnight. The tests were conducted at seven day intervals, and each was preceded by a ten hour fast. During the three days before each test the subjects received meals containing no less than 300 gm. carbohydrate per day. Blood samples were drawn at 0, 15, 30, 60, 90, 120, and 180 minutes. A clear circadian variation occurred in the blood glucose levels, with lower values in the morning and higher values at 6 p.m. and midnight. The insulin profiles showed a trend toward lower afternoon and night values, with a noon peak. The afternoon insulin-glucose ratios were significantly lower. HGH values were inconsistent and tended toward higher afternoon and night basal levels. The results confirm the existence of a circadian variation in the blood glucose response to oral glucose loads in healthy men. This might in turn result from a circadian variation in the insulin response, probably secondary to changes in the pancreatic β cell sensitivity to glucose. This basic mechanism is believed to sustain the conditioning influence of other hormones, HGH being one of them.

Changes induced by a fructose-rich diet on hepatic metabolism and the antioxidant system

AIMS The effect of a three-week fructose-rich diet (FRD) upon gene expression, protein and activity levels of liver antioxidant system and carbohydrate metabolism was studied. MAIN METHODS Serum glucose (fasting and after a glucose load), triglyceride and insulin levels of normal male Wistar rats were measured. In liver, we measured gene/protein expression and enzyme activity of catalase (CAT), copper-zinc-superoxide dismutase (CuZnSOD) and glutathione peroxidase (GSHPx); reduced glutathione (GSH); protein carbonyl content; thiobarbituric acid reactive substances (TBARS) content and microsomal membrane susceptibility to lipid peroxidation; glucokinase (GK), glucose-6-phosphatase (G-6-Pase) and glucose-6-phosphate dehydrogenase (G-6-PDH) activity; and glycogen, pyruvate, lactate and triglyceride content. KEY FINDINGS Similar body weights and caloric intake were recorded in both groups. FRD rats had higher serum glucose, insulin and triglyceride levels, molar insulin:glucose ratio, HOMA-IR values and impaired glucose tolerance, whereas CAT, CuZnSOD and GSHPx relative gene expression levels were significantly lower. CAT and CuZnSOD protein expression, CAT activity and GSH content were also lower, while protein carbonyl content was higher. No differences were recorded in CuZnSOD, MnSOD and GSHPx activity, TBARS content and membrane susceptibility to lipid peroxidation. Glycogen, lactate and triglyceride content and GK, G-6-Pase and G-6-PDH activity were significantly higher in FRD rats. SIGNIFICANCE In the presence of oxidative stress, the liver exhibits changes in the carbohydrate and lipid metabolic pathways that would decrease reactive oxygen species production and their deleterious effect, thus inducing little impact on specific antioxidant mechanisms. This knowledge could facilitate the design and implementation of strategies to prevent oxidative stress-induced liver damage.

Liver glucokinase: An overview on the regulatorymechanisms of its activity

Blood glucose is the primary cellular substrate and in vivo must be tightly maintained. The liver plays a key role in glucose homeostasis increasing or decreasing glucose output and uptake during fasting and feeding. Glucokinase (GCK) is central to this process. Its activity is modulated in a coordinated manner via a complex set of mechanisms: in the postprandial period, the simultaneous rise in glucose and insulin increases GCK activity by enhanced gene expression, changes in cellular location, and interaction with regulatory proteins. Conversely, in the fasting state, the combined decrease in glucose and insulin concentrations and increase in glucagon concentrations, halt GCK activity. Herein we summarize the current knowledge regarding the regulation of hepatic GCK activity.

Fructose-rich diet-induced abdominal adipose tissue endocrine dysfunction in normal male rats.

We have currently studied the changes induced by administration of a fructose-rich diet (FRD) to normal rats in the mass and the endocrine function of abdominal (omental) adipose tissue (AAT). Rats were fed ad libitum a standard commercial chow and tap water, either alone (control diet, CD) or containing fructose (10%, w/vol) (FRD). Three weeks after treatment, circulating metabolic markers and leptin release from adipocytes of AAT were measured. Plasma free fatty acids (FFAs), leptin, adiponectin, and plasminogen activator inhibitor-1 (PAI-1) levels were significantly higher in FRD than in CD rats. AAT mass was greater in FRD than in CD rats and their adipocytes were larger, they secreted more leptin and showed impaired insulin sensitivity. While leptin mRNA expression increased in AAT from FRD rats, gene expression of insulin receptor substrate, IRS1 and IRS2 was significantly reduced. Our study demonstrates that administration of a FRD significantly affects insulin sensitivity and several AAT endocrine/metabolic functions. These alterations could be part of a network of interacting abnormalities triggered by FRD-induced oxidative stress at the AAT level. In view of the impaired glucose tolerance observed in FRD rats, these alterations could play a key role in both the development of metabolic syndrome (MS) and β-cell failure.

Decreased Ca2+-ATPase Activity After Glycosylation of Erythrocyte Membranes In Vivo and In Vitro

Erythrocyte membranes drawn from diabetic patients with poor metabolic control have increased protein glycosylation and decreased Ca2+-ATPase activity. A significant relationship was found between these two parameters. Similar results were obtained when protein glycosylation and Ca2+-ATPase activity were measured in membranes from normal erythrocytes preincubated with glucose. In this condition, both parameters showed a clear time and dose dependence. Incubation of erythrocyte membranes instead of intact erythrocytes with glucose and glucose-6-phosphate strongly suggests that only the glycosylation of the membrane inner-surface proteins can affect Ca2+-ATPase activity. The simultaneous presence of 10 mM glucose and 5 mM ATP in the incubation medium did not affect the degree of erythrocyte membrane protein glycosylation but significantly blocked the inhibitory effect of glucose on Ca2+-ATPase activity. However, 5 mM ATP only partially blocked the inhibitory effect of 100 mM glucose, suggesting a competitive mechanism of glucose and ATP for the enzyme active site. Our results show that glycosylation of erythrocyte membrane proteins significantly inhibits Ca2+-ATPase activity. This effect could contribute to the development of the capillary closure process observed in diabetic patients. Furthermore, it could represent an index of a general impairment of enzyme function arising in cells chronically exposed to high glucose levels.

Evaluation of the effectiveness of an ambulatory teaching/treatment programme for non-insulin dependent (type 2) diabetic patients

The aim of this study was to evaluate the effect of a structured teaching/treatment programme on the clinical and metabolic control of non-insulin-dependent (type 2) diabetic patients. The programme was aimed at improving the overall treatment quality in these patients through measures involving self-care, diet, exercise and weight reduction. Four theoretical-practical teaching units were given once a week to group of 5–8 ambulatory patients by previously trained general practitioners. Clinical and biochemical parameters were recorded at the beginning of the course and 1 year after its completion in 40 patients attending the programme and in 39 patients of similar clinical characteristics under conventional diabetes treatment, but receiving no structured teaching before or during the survey period (control group). The drop-out percentage in the intervention group (25%) was significantly lower than in the control group (45%),P<0.05, suggesting an incentive toward greater compliance in the former. At the end of the 1-year follow-up, the mean differences observed in the control and in the intervention groups were: body weight loss −2.4±0.5 kg vs −0.4±0.5 (P<0.001); haemoglobin HbA1 −0.2%±0.4% vs +0.8±0.4% (NS); number of daily oral hypoglycaemic agent intake −1.4±0.2 vs +0.9±0.2 tablets (P<0.001). Our results strongly suggest that this programme, applied through family doctors, may constitute an efficient tool to improve the compliance and clinico-metabolic control of type 2 patients at the primary health care level.

Type 2 diabetes patients educated by other patients perform at least as well as patients trained by professionals.

Diabetes education can improve the quality of care of people with diabetes, but many organizations are not equipped to manage its implementation. Involving people with diabetes in the education process can overcome the problem. Thus, we compared clinical, metabolic and psychological outcomes in people with type 2 diabetes 1 year after attending a structured diabetes education programme implemented by professional educators versus the same programme implemented by trained peers with diabetes that also provided ongoing peer support.