PHYTOCHEMICAL INVESTIGATION OF METHANOLIC EXTRACT OF COCCINIA INDICA LEAVES

The food glycemic index is a measure of the level of elevated blood glucose in food. In the face of the growing population of diabetic patients, how to play a significant therapeutic role through dietary intervention with different glycemic index has become a new research hotspot. In recent years, several studies have shown that different glycemic index diets have important effects on blood glucose, body weight and blood lipid levels in diabetic patients. Compared with high-glycemic index diet, low-glycemic index diet can reduce blood glucose level and maintain blood glucose stability in diabetic patients, and play an indispensable role in weight loss and decrease of blood lipid levels. And low-glycemic index diet can also reduce the risk of pregnancy complications in gestational diabetes, so it has gradually become the mainstream dietary intervention strategy for diabetic patients. Key words: Low-glycemic index; Type 2 diabetes mellitus; Gestational diabetes mellitus; Blood glucose; Blood lipid

The growing pandemic of childhood obesity has led to marked increases in the incidence and prevalence of type 2 diabetes mellitus (DM) and has further complicated the differentiation between type 2 and type 1 DM because more children with type 1 DM are overweight at time of diagnosis. In addition, numerous studies have demonstrated β-cell autoimmunity in children with type 2 DM. (1)After completing this article, readers should be able to:Type 2 diabetes mellitus (DM), historically considered a serious chronic medical condition only for older individuals, now has an increased prevalence in children and adolescents. The estimated overall incidence of type 2 DM is 22 cases per 100,000 youth or approximately 3600 youth diagnosed with the condition each year. (2) From a public health perspective, DM is the seventh leading cause of death in the United States, a figure that is likely underestimated. (3) The total cost to treat DM in both adults and children is approximately $174 billion per year, and medical expenses for individuals with diagnosed DM are 2.3 times higher than for those without DM. (3) The clinical and financial burdens of DM are increased by the complications and comorbidities of the disease. Because complications of DM develop and worsen during the disease, (2) it is important to effectively recognize and manage type 2 DM early when it is diagnosed during childhood and adolescence.DM represents a group of endocrine disorders characterized by hyperglycemia caused by defective insulin secretion, defective insulin action, or both. (4) The original division into 2 types was based on age at presentation and dependence on insulin. Now categories of DM (Table 1) are differentiated by their known underlying pathophysiologic characteristics. All forms of DM ultimately lead to hyperglycemia, although there may be overlap in the fundamental pathologic processes in each patient.Recent epidemiologic studies have demonstrated that more than 20% of new cases of DM in children and adolescents are due to type 2 DM. (5) The incidence of type 2 DM in children has increased in part because of the epidemic of childhood obesity and the associated insulin resistance, although the actual incidence of type 2 DM in children is likely higher than reported because of underdiagnosis.The incidence of type 2 DM increases with age. The SEARCH for Diabetes in Youth study demonstrated that the incidence of type 2 DM in children age 10 to 19 years was 42 per 100,000 youth compared with 1 in 100,000 youth among children age 0 to 9 years. (2) The peak age at onset of type 2 DM in children coincides with pubertal timing because the mean age at diagnosis is 12 to 16 years. (6) Females have a higher incidence of type 2 DM than males, (5) likely because girls are more insulin resistant and carry more subcutaneous fat than boys. (7)Type 2 DM disproportionately affects racial and ethnic minorities. American Indian youth have the highest incidence at 174 per 100,000. Black youth also have a particularly high incidence of 105 per 100,000 compared with 19 per 100,000 in non-Hispanic whites. (2)Epidemiologic studies report that children born to mothers with gestational diabetes are at greater risk of developing type 2 DM. (8) Breastfeeding appears to have protective effects against the development of type 2 DM. (9)The cause of type 2 DM is multifactorial, but the high concordance rate among monozygotic twins (1) and the frequent association with a family history of DM (10) suggest a genetic component. Between 74% and 100% of patients with type 2 DM have a first- or second-degree relative with the disease, in contrast to only 5% of patients with type 1 DM with a family history of type 1 DM. (6) Recent studies have identified multiple genetic loci that are associated with higher risk of type 2 DM. For example, polymorphisms in the TCF7L2 gene result in impaired insulin secretion and defective insulin processing, which confer a 1.4 times increased risk of type 2 DM. (1) More genetic markers are being identified with improvements in genetic testing.Glucose metabolism is tightly regulated by several processes, including sensing of glucose concentration, insulin synthesis, and secretion by pancreatic β-cells; suppression of hepatic glucose output; and insulin action on stimulated glucose uptake by the liver, intestines, and skeletal muscle. Hyperglycemia can result from derangements in any of these processes.Typically, type 1 DM and type 2 DM are conceptualized on a spectrum. Type 1 DM results from immune-mediated destruction of β-cells, leading to insulinopenia. Type 2 DM is the result of obesity-mediated insulin resistance and non–immune-mediated deficiency in insulin secretion.The pathogenesis of type 2 DM is complex and involves interactions between genetic and environmental factors. The core defect is varying degrees of insulin resistance and subsequent progressive insulinopenia. Other factors associated with obesity, such as elevated plasma free fatty acid concentrations and increased inflammatory markers, further inhibit β-cell insulin production and insulin-mediated glucose uptake. This leads to a cycle of worsening hyperglycemia and further metabolic derangement.A theory called the accelerator hypothesis suggests that obesity and weight gain contribute significantly to β-cell stress and confer earlier onset of all types of DM. Obesity is increasingly being accepted as a contributor to β-cell failure in genetically susceptible children, and increasing evidence suggests the influence of obesity in abnormal immune modulation. (1)During the past 30 years Americans have increased their total caloric intake by an additional 300 kcal/d. (11) Consumption of juices and sugar-sweetened beverages is a major source of these additional calories in the diet of children and adolescents (12) and is strongly associated with an increased risk of obesity and type 2 DM. (7) In addition, fewer children and adolescents are participating in recommended levels of physical activity.The association between lower birth weight and type 2 DM suggests that in utero programming may increase the risk of type 2 DM. (13) A thrifty-phenotype hypothesis suggests that poor fetal nutrition produces a postnatal metabolism that is adapted to poor but not plentiful nutrition. This programming contributes to insulin resistance and can predispose the development of type 2 DM in the context of excess nutrition and obesity. (14)Because up to 24% of children and adolescents with type 1 DM are overweight at diagnosis, (6) differentiating between type 2 DM and type 1 DM has become more difficult. (15) Further complicating the clinical delineation is the presence or absence of autoimmunity. The SEARCH for Diabetes in Youth Study measured the presence of glutamic decarboxylase (GAD) antibodies among diabetic patients. Positive GAD antibodies were found in 21% of patients with type 2 DM older than 10 years. (5) The Treatment Options for Type 2 DM in Adolescents and Youth (TODAY) study, a multicenter clinical trial, evaluated the presence of GAD and insulinoma-associated protein 2 antibodies. Of patients with diagnosed type 2 DM, 9.8% were antibody positive, 5.9% were positive for a single antibody, and 3.9% were positive for both antibodies. Those patients diagnosed as having type 2 DM who were antibody positive were more likely to be white and male and had a lower body mass index than antibody-negative patients. (16) A significant controversy exists regarding the classification of antibody-positive type 2 DM, with many authors maintaining that antibody-positive type 2 DM should be considered early type 1 DM and treated as such.The presenting symptoms of type 1 and type 2 DM can be similar and include polyuria, polydipsia, and polyphagia. Weight loss can be present in both types of DM. Clinical signs to suggest type 2 DM include overweight body habitus, with more than 85% of children with type 2 DM considered overweight or obese at the time of diagnosis. (6) Acanthosis nigricans, a darkened, thick, velvety appearance to the skin found typically in folds or creases, is present in 90% of patients with type 2 DM and can be the most easily visible clinical indicator of insulin resistance. (7) The frequency of acanthosis nigricans in obese adolescents or hyperinsulinemic children varies considerably by ethnicity. Up to 90% of obese or hyperinsulinemic children in Native American populations had acanthosis nigricans, whereas it was present in less than 5% of non-Hispanic white counterparts. (7) Clinicians can look for acanthosis nigricans in the nape of the neck, axilla, groin, and over flexor surfaces. The presence of ketoacidosis, normally found in patients with type 1 DM, does not rule out type 2 DM. Some reports indicate that up to 25% of children and adolescents with type 2 DM present with diabetic ketoacidosis. (17)Type 2 DM generally has a more insidious onset than type 1 DM, and many patients may be asymptomatic at presentation. However, because of the potentially long-standing hyperglycemia, patients may already have evidence of microvascular and macrovascular complications at the time of diagnosis. (10)Overall, the clinical distinction between type 1 DM and type 2 DM is increasingly obscured, especially with the increasing obesity pandemic. Clinicians must weigh the evidence to support their diagnosis and consider the potential outcomes of misclassification. In the case of significant hyperglycemia, diabetic ketoacidosis, and/or positive antibodies, it may be prudent to treat patients as having type 1 DM and wean insulin therapy if the future clinical course dictates.The criteria for diagnosis of DM were based on data to delineate risk for the development of retinopathy, a microvascular complication of DM, and are included in Table 2. (10) In 2009, an international expert committee convened and added an additional criterion for diagnosis, a hemoglobin A1c (HbA1c) level greater than 6.5% (0.07). (10)Indications to test for type 2 DM according to the Type 2 DM Consensus Panel are given in Table 3. Testing should begin at age 10 years or at the age of pubertal onset, whichever comes first, and should be repeated every 3 years. (18) The preferred method is to measure a fasting plasma glucose level, but a 2-hour plasma glucose level measured during an oral glucose tolerance test (OGTT) can be an alternative. (6)The American Diabetes Association (ADA) recommends that treatment of all children with DM should include routine follow-up every 3 months with a diabetes care team. (18) This team should include nutritional, psychological, and educational support and a medical professional experienced with DM care. The patient's self-management involves monitoring of blood glucose level, medication compliance, attention to dietary intake, and physical activity. Psychosocial considerations and medical compliance must also be addressed to ensure optimal success with therapy. The HbA1c level should be measured every 3 months during outpatient visits, and the goal HbA1c should be less than 7%. (18)(19)(20) Assessment of lipids, liver function tests, microalbuminuria, and signs and symptoms of sleep apnea should occur at diagnosis and annually. (19) Coordination between the diabetes care team and the primary care practitioner ensures a complete medical home for the child or adolescent.Treatment should be guided by the acuity of the clinical presentation. If a patient is acutely ketotic, dehydrated, or acidotic, intravenous hydration and insulin administration with inpatient admission are warranted. If the presentation is less acute, subspecialty referral, outpatient education, and use of oral medications can be initiated. Once the patient is clinically stable, treatment of type 2 DM is dually focused on weight management and minimizing complications associated with hyperglycemia.Lifestyle modification is an essential component of the management of type 2 DM and includes an emphasis on proper diet and exercise to maintain a healthy weight while preserving linear growth. For optimal management, lifestyle modification should be centered around the family unit and not strictly on individual patients. (20)Pharmacologic therapy addresses various aspects of the pathogenesis of type 2 DM (Figure) by reducing insulin resistance, increasing insulin secretion, slowing postprandial glucose absorption, or supplementing inadequate secretion of insulin. Metformin, a biguanide, is the only US Food and Drug Administration (FDA)–approved oral medication for treatment of type 2 DM in children older than 10 years and is considered first-line therapy in nonacute presentations. The mechanism of action is to decrease hepatic glucose production and enhance insulin-mediated glucose uptake in muscle and adipose cells. Adverse effects include transient abdominal pain, diarrhea, and nausea, although it is generally well tolerated. Metformin should not be given to patients with renal insufficiency, liver disease, or cardiac or respiratory insufficiency. Patients should be warned to discontinue metformin therapy before receiving intravenous contrast for radiographic studies because of the increased risk of lactic acidosis. In adults there is evidence that metformin can normalize blood glucose levels, decrease cholesterol levels, and reduce hypertension. Metformin can also be used to normalize ovulatory abnormalities in patients with polycystic ovarian syndrome. It is available in a liquid formulation and as an extended-release formulation, which can aid compliance and potentially reduce adverse effects. The recommended starting dose for metformin is 500 mg given orally once daily, with a maximum dose of 2000 mg per day.Insulin is used to attain early normalization of glycemic control, especially in patients who are acutely ill or have significant hyperglycemia, and insulin therapy should be started in all patients who present with diabetic ketoacidosis. Recent American Academy of Pediatrics clinical practice guidelines on the management of newly diagnosed type 2 DM recommend that insulin therapy be initiated in patients who have a random blood glucose level greater than 250 mg/dL (13.9 mmol/L) or whose HbA1c level is greater than 9%. (20) Once the diagnosis of type 2 DM is determined, insulin therapy can often be reduced as metformin therapy is initiated. Adverse effects of insulin can include weight gain from its anabolic effect on metabolism. Hypoglycemia, a potential adverse effect, is not as common among patients with type 2 DM.Other therapies, although not FDA approved for patients younger than 18 years, can be used by the diabetes management team to improve glycemic control. Sulfonylureas (glyburide, glipizide, and glimepiride) directly increase insulin secretion, so they are most useful when there is residual β-cell function. Major adverse effects include hypoglycemia and weight gain. Glucosidase inhibitors (acarbose and miglitol) reduce absorption of carbohydrates in the upper small intestine. They can lower HbA1c levels by 0.5% to 1%, and the major adverse effects are gastrointestinal intolerance and flatulence. Incretins (exenatide) are designed to increase postprandial insulin secretion. Exenatide is administered as a twice-daily injection. Adverse effects include nausea, vomiting, diarrhea, dyspepsia, jitteriness, dizziness, headaches, and hypoglycemia, especially if given with a sulfonylurea. Thiazolidinediones (rosiglitazone and pioglitazone) increase insulin sensitivity in muscle, adipose tissue, and the liver. In isolation, they can reduce HbA1c levels by 0.5% to 1.3%. Results from the TODAY study demonstrated that metformin in combination with rosiglitazone was more successful than metformin alone or metformin with lifestyle modification in preventing an increase in HbA1c levels above 8% (0.08). (20) There is some evidence that this combination may improve lipid profiles by lowering triglyceride levels and increasing high-density lipoprotein levels. (21) Adverse effects include edema, weight gain, and anemia and may infer additional cardiac risk (Figure).The risk of DM-related complications is directly related to the duration of disease. Prompt diagnosis and appropriate therapy are paramount in reducing this risk. Because of its insidious onset, many patients with type 2 DM have evidence of complications at the time of diagnosis. Among a sample of 100 Pima Indians with type 2 DM, 18% had hypertension, 7% had dyslipidemia, and 22% had microalbuminuria at the time of diagnosis. (22) Microvascular complications of type 2 DM include nephropathy, retinopathy, and neuropathy. Macrovascular complications include hypertension and hyperlipidemia, which can lead to cardiovascular disease. The ADA recommends that patients with type 2 DM have blood pressure measurements performed at every routine diabetes visit. (18) In the UK Prospective Diabetes Study, hypertension was found to be a more significant predictor of cardiovascular disease than blood glucose control. This study also found a 25% reduction in the risk of microvascular complications when the average HbA1c level decreased from 7.9% to 7.0%. (23)Patients should be screened for retinopathy with a dilated eye examination near the time of diagnosis and then yearly afterward. A lipid profile should be performed shortly after diagnosis, once glycemic control is attained, and should be performed annually thereafter. Urine microalbumin should be measured at diagnosis to assess for early nephropathy and followed up yearly. (18)Primary public health prevention efforts should target the general population to limit the prevalence of obesity. Secondary prevention should focus on screening those children who are at high risk for the development of type 2 DM (Table 2). Tertiary prevention in patients with type 2 DM should address reduction of complications.The authors wish to acknowledge Babalola Faseru, MD, MPH, assistant professor, Department of Preventive Medicine and Public Health, University of Kansas School of Medicine, and Naim Mitre, MD, Naim Mitre, MD, medical director of clinical services, assistant fellowship program director, assistant professor of pediatrics, Division of Endocrine/Diabetes, Department of Pediatrics, University of Missouri-Kansas City/Children's Mercy Hospital.

On the basis of strong research evidence and consensus, type 1 diabetes mellitus (DM) remains the most common form of DM in children and adolescents. The incidence of type 2 DM in the pediatric population is rapidly increasing because of the obesity epidemic, and minority groups are disproportionately affected. (2) (10) (19) On the basis of some research evidence and consensus, it can be challenging to initially differentiate between type 2 DM and type 1 DM clinically because of the increased prevalence of obesity, the complex interplay of autoimmunity and obesity, and common symptoms at presentation. (1) (10) (19) Significant evidence and consensus support a genetic basis for the development of type 2 DM in children. Physicians should routinely screen at risk children older than age 10 years for DM. Screening criteria include obesity, a family history of type 2 DM, a minority racial or ethnic background, acanthosis nigricans, or other diseases associated with insulin resistance, including polycystic ovary syndrome, hypertension, or dyslipidemia. (1) (10) (18) (19) On the basis of consensus, diagnosis of type 2 DM can be confirmed by an elevated fasting blood glucose level greater than 126 mg/dl (7.0 mmol/L), an elevated 2-hour plasma glucose greater than 200 mg/dL (11.1 mmol/L) on an oral glucose tolerance test, an elevated random blood glucose greater than 200 mg/dL (11.1 mmol/L), or a hemoglobin A1c level greater than 6.5% with suggestive symptoms. (10) According to strong research evidence and consensus, once the diagnosis has been made, treatment should be based on the acuity of presentation and should focus on lifestyle modification and on normalizing hyperglycemia to minimize complications. Metformin is currently first-line treatment for type 2 DM in children and adolescents older than age 10 years who present nonacutely. (18) (19) Strong research evidence and consensus demonstrate that because type 2 DM has an insidious onset, microvascular and macrovascular complications can be present at the time of diagnosis. Patients should be screened for the presence of complications when the diagnosis of type 2 DM is made and in follow-up. (6) (10).

Gestational diabetes mellitus (GDM) is one of the most common complications of pregnancy, and women with GDM are at increased risk for type 2 diabetes mellitus1. Uncomplicated pregnancy is characterized by insulin resistance and enhanced insulin secretion as a compensatory mechanism to maintain normal glucose tolerance (NGT). However, previous studies showed that in women with GDM during pregnancy, the decreased sensitivity of insulin is at a similar level to NGT, but with more pronounced insulin resistance than NGT. These phenomena might contribute to hyperglycemia in addition to defective insulin release2. Furthermore, women with a history of GDM have been considered a high‐risk group for diabetes mellitus. A study reported from Korea showed that Korean women with a history of GDM have a four‐ to fivefold greater risk of developing postpartum diabetes than the general population (Figure 1). The incidence of type 2 diabetes mellitus within 30 years), prepregnant body mass index (>23 kg/m2), family history of type 2 diabetes mellitus, fasting glucose level at the time of GDM diagnosis (>5.8 mmol/L) and early diagnosis of GDM during pregnancy (<26 weeks)3. In contrast, the putative risk factors for type 2 diabetes mellitus in the Korean population include (but are not limited to) old age, urban living, female sex, obesity, smoking, family history of diabetes, impaired liver function, metabolic syndrome, elevated blood pressure and increased triglycerides4. Although all the risk factors have yet to be identified, the aforementioned variables are the key risk factors for diabetes mellitus in Koreans. Most of these risk factors have also been identified as key risk factors in other places including Europe, South America, North America and Africa. As previously mentioned, some of the risk factors, such as family history of diabetes, lipid profile, high blood pressure and obesity, are common risk factors of both type 2 diabetes mellitus and GDM. Thus, one could question whether GDM is another type of diabetes mellitus or a simple identification of existing type 2 diabetes mellitus during pregnancy when physical, metabolic and psychological changes occur dramatically. It was very difficult to answer the question until the advancement of the Genome‐Wide Association Study (GWAS), which enabled the investigation of genetic background. The genome‐wide association (GWA) approach is an emerging methodology that allows us to identify genetic variants with specific loci that predispose individuals to complex traits and/or diseases.

BACKGROUND: Hyperglycemia in pregnancy is associated with short- and long-term implications for children. Nevertheless, the effects of different types of diabetes mellitus and treatment methods on the neonatal outcomes are to be investigated. AIM: The aim of this study was to evaluate the contribution of different types of maternal diabetes mellitus to the risk of adverse neonatal outcomes. MATERIALS AND METHODS: This retrospective cohort study included women (n = 3261) who delivered at the Research Institute of Obstetrics, Gynecology and Reproductology named after D.O. Ott, Saint Petersburg, Russia in 2008–2017. The following comparison groups were used: type 1 diabetes mellitus (n = 506; 1a, continuous subcutaneous insulin injections; 1b, multiple daily insulin injections), type 2 diabetes mellitus (n = 229; 2a, diet; 2b, insulin therapy), gestational diabetes mellitus (n = 2387; 3a, diet; 3b, insulin therapy), and control (n = 139). The main birth outcomes assessed included weight and length of newborns, Apgar score at birth and at 5 minutes after birth, and pathological conditions such as fetal macrosomia, syndrome of infant of mother with gestational diabetes mellitus or diabetic mother (P70.0–P70.1), light (P05.0) or small for gestational age (P05.1), intrauterine growth restriction, prematurity (P07), neonatal hypoglycemia (P70.4), and neonatal respiratory distress syndrome (P22). The secondary birth outcomes assessed included birth trauma (P10–P15), stillbirth (P95), disturbances of cerebral status of newborn (P91), and congenital malformations, deformations and chromosomal abnormalities (Q00–Q99). RESULTS: Pregestational diabetes mellitus is strongly associated with adverse neonatal outcomes. Type 1 diabetes mellitus women had the highest risks for fetal macrosomia and diabetic fetopathy, neonatal hypoglycemia, prematurity, and congenital malformations (odds ratio 3.54, 20.2, 5.59, 4.24 and 3.92 respectively). In type 2 diabetes mellitus patients, the risks of low birth weight, intrauterine growth restriction and birth trauma (odds 9.14, 5.42 and 6.3 respectively) were higher. For women with gestational diabetes mellitus, these risks were lower. CONCLUSIONS: This study provides a comprehensive analysis of the major neonatal pathology in patients with different types of diabetes mellitus, taking into account the treatment method. Preconception care and optimal glycemic control are necessary to reduce the risk of obstetric and perinatal complications in women with pregestational types of diabetes mellitus. Further research into the health status of this cohort of children at a later age is required.

Introduction. Pregnancy complicated by diabetes mellitus (DM) is associated with a high risk of adverse perinatal outcomes (prematurity, diabetic fetopathy). These complications are caused by chronic intrauterine fetal hypoxia associated with the enhancement of oxidative stress. Imbalance between reactive oxygen species production and the activity of the antioxidant system plays an important role in the pathogenesis of various DM types during pregnancy. Objective. The aim of this study was to evaluate oxidative stress markers in pregnant women with pre-pregnancy DM (PGDM) type 1 or 2, with gestational diabetes mellitus (GDM), and in the control group without hyperglycemia at 37-41 weeks of pregnancy; as well as to assess the severity of oxidative stress depending on the DM type. Materials and methods. 3-Nitrotyrosine and malondialdehyde levels, catalase and total antiradical activities were determined in the maternal and cord blood serum of 94 pregnant women. The serum concentration of 3-nitrotyrosine was measured using the ELISA method; malondialdehyde level, catalase activity, and antiradical activity were measured by colorimetric methods. Results. Increased 3-nitrotyrosine and malondialdehyde levels were observed in the PGDM group compared to the other study groups (GDM and control groups). Total antiradical activity increased in the PGDM and GDM groups, catalase activity not changing in all the study groups. Conclusions. DM during pregnancy is associated with the enhancement of oxidative stress, which can lead to the development of adverse perinatal outcomes. Moreover, patients with PGDM showed activation of oxidative stress that was more pronounced compared to the control group and the group of patients with GDM.

BackgroundBlood glucose levels during pregnancy may reflect the severity of insulin secretory defects and/or insulin resistance during gestational diabetes mellitus (GDM) pregnancy. We hypothesized that suboptimal glycemic control in women with GDM could increase the risk of postpartum type 2 diabetes mellitus (T2DM) or prediabetes. Our objective was to evaluate the impact of plasma glucose levels throughout GDM pregnancy on the risk of postpartum T2DM or prediabetes.MethodsThe medical records of 706 women with GDM who underwent a postpartum 75-g, 2-hour oral glucose tolerance test at our institution between January 2011 and December 2018 were reviewed. These women were classified into 2 groups according to glycemic control during pregnancy: ≤ 1 occasion of either fasting glucose ≥ 95 mg/dL or 2-hour postprandial glucose ≥ 120 mg/dL was defined as optimal glycemic control or else was classified as suboptimal glycemic control. Rates of postpartum T2DM and prediabetes were compared between women with optimal (n = 505) and suboptimal (n = 201) glycemic control.ResultsThe rates of postpartum T2DM and prediabetes were significantly higher in the suboptimal glycemic control group than in the optimal glycemic control group: 22.4% vs. 3.0%, P < 0.001 for T2DM and 45.3% vs. 23.5%, P < 0.001 for prediabetes. In a multivariate analysis, suboptimal glucose control during pregnancy was an independent risk factor for developing either postpartum T2DM or prediabetes. The adjusted odds ratios were 8.4 (95% confidence interval, 3.5–20.3) for T2DM and 3.9 (95% confidence interval, 2.5–6.1) for prediabetes.ConclusionOur findings suggest that blood glucose levels during GDM pregnancy have an impact on the risk of postpartum T2DM and prediabetes.

Concept of Diabetes Mellitus: Diabetes mellitus is a group of diseases associated with various metabolic disorders, the main feature of which is chronic hyperglycemia due to insufficient insulin action. Its pathogenesis involves both genetic and environmental factors. The long‐term persistence of metabolic disorders can cause susceptibility to specific complications and also foster arteriosclerosis. Diabetes mellitus is associated with a broad range of clinical presentations, from being asymptomatic to ketoacidosis or coma, depending on the degree of metabolic disorder.

In many parts of the world the number of pregnancies in women with Type 2 diabetes mellitus (DM) now exceeds that in women with Type 1 DM, but there are few data published on perinatal mortality in Type 2 DM. This study reports observational data on perinatal mortality in Type 2 DM from a population with a high background rate of this disorder. Over a 12-year period (1985-1997) at the Diabetes Clinic at National Women's Hospital, Auckland, there were 434 pregnancies in women with Type 2 DM (256 known and 178 diagnosed with gestational diabetes mellitus (GDM), but confirmed to have Type 2 DM early post-partum), 160 pregnancies in women with Type 1 DM and 932 in women with GDM. Perinatal mortality was classified as either intermediate fetal death (20-28 weeks' gestation), late fetal death (28 weeks' gestation to term) or early neonatal death (up to 1 month post-partum). The perinatal mortality in Type 2DM was 46.1/1,000, significantly higher than the rates for the general population (12.5), Type 1 DM (12.5) and GDM (8.9) (P < 0.0001). Congenital malformations accounted for only 10% of the perinatal mortality. There was a seven-fold increase in the rate of late fetal death and 2.5-fold increase in the rates of intermediate fetal and late neonatal death. Subjects with Type 2 DM were significantly older and more obese than subjects with Type 1 DM, and presented later to the diabetes service. Perinatal mortality in Type 2 DM is significantly increased, mainly owing to an excess of late fetal death. Maternal factors such as obesity may be important contributors to the high perinatal mortality. Women diagnosed with GDM who have unrecognized Type 2 DM are also at high risk, but perinatal mortality is low in women with milder degrees of glucose intolerance in pregnancy.

Adherence to self-glucose monitoring recommendations and perinatal outcomes in pregnancies complicated by diabetes mellitus

Objective To explore the effects of emergent laparoscopic appendectomy on pancreatic endocrine function of patients with acute suppurative appendicitis combined with type 2 diabetes mellitus. Methods The clinical data of 76 patients with suppurative appendicitis combined with type 2 diabetes mellitus who were admitted to the Yongchuan Hospital of Chongqing Medical University between October 2012 and October 2014 were retrospectively analyzed. Among the 76 patients receiving emergent appendectomy, 41 patients receiving laparoscopic appendectomy were allocated to the laparoscopy group and 35 patients receiving open appendectomy were allocated to the open surgery group. The intraoperative conditions of patients were observed. The levels of serum C-peptide, insulin and blood glucose at preoperative minute 15 (t1) , intraoperative minute 15 (t2) , intraoperative minute 30 (t3) and postoperative minute 30 (t4) were detected by enzyme-linked immunosorbent assay (ELISA) . The recovery indicators of patients were analyzed. The patients were followed up by telephone interview till December 2014. Measurement data with normal distribution were presented as ±s. Comparison between groups was analyzed by the independent samples t-test and repeated measures ANOVA. Count data were compared by the Fisher exact probability. Results All the patients underwent successfully the operations. The operation time and the volume of intraoperative blood loss in the laparoscopy group were (50 ±7) minutes and (8. 4 ±3.4) mL, which were not significantly different from (52 ±7) minutes and (7.7 ±2. 9) mL in the open surgery group (t =1.291, 1.042, P >0.05) . Serious adhesions of tissues around the appendix in the laparoscopy group were detected in 8 patients, which was not significantly different from 11 patients in the open surgery group (P >0.05) . The results of the serologic test showed that the levels of serum C-peptide between t1 and t4 were (62. 5 ±3.3) μg/ L, (70. 7 ± 2. 9) μg/ L, (86. 5 ± 3.4) μg/ L and (68.1 ± 2.6) μg/ L in the laparoscopy group and (63.8 ± 2. 8 ) μg/ L, (95.6 ±5. 1) μg/ L, (106. 6 ±2.3) μg/ L and (67.5 ±4.9) μg/ L in the open surgery group, respectively. The levels of insulin between t1 and t4 were (13.1 ± 1.0) mU/ L, (14.0 ±1.1) mU/ L, (15.1 ± 1. 2) mU/ L and (13. 5 ± 1. 1) mU/ L in the laparoscopy group and (13. 3 ±0. 4) mU/ L, (15. 4 ±0. 6) mU/ L, (18. 2 ±0.7) mU/ L and (13.5 ±0. 4) mU/ L in the open surgery group, respectively. The levels of blood glucose between t1 and t4 were (7.8 ±1.0) mmol/ L, (8.3 ± 1.0) mmol/ L, (8.9 ± 1.0) mmol/ L and (8.1 ± 1.0) mmol/ L in the laparoscopy group and (7.8 ± 0.4) mmol/ L, (8.7 ± 0.5) mmol/ L, (10.1 ± 0.4) mmol/ L and (7.9 ± 0. 5 )mmol/ L in the open surgery group, respectively. There were significant differences in the changing trends of serum C-peptide, insulin and blood glucose between the 2 groups (F =378.917, 286.602, 118.199, P 0.05) . The duration of postoperative abdominal pain in the laparoscopy group was(1. 5 ±0.6) days ,which was significantly different from (2.5 ±0. 7) days in the open surgery group (t =-6.367, P <0.05) . The wound infection and fever in the laparoscopy group were detected in 6 and 10 patients, which were significantly different from 14 and 22 patients in the open surgery group (P <0.05) . The duration of hospital stay in the laparoscopy group and in the open surgery group were (5.2 ± 0.4) days and (6.3 ± 0.8) days, respectively, showing a significant difference between the 2 groups (t =7.796, P <0.05) . All the patients were followed up for a median time of 8 months (range, 2- 18 months) , without adhesive intestinal obstruction, abdominal pain, abdominal distension and appendix stump inflammation. Conclusion The emergency laparoscopic appendectomy compared with the open surgery would be less affected on pancreatic endocrine function of patients with acute suppurative appendicitis combined with type 2 diabetes mellitus, with an advantage of better postoperative recovery. Key words: Appendicitis; Diabetes mellitus, type 2; Laparoscopy

Diabetes mellitus is an endocrinological metabolic disorder in which patients have elevated blood glucose levels compared to normal healthy individuals. Type 1 and type 2 diabetes mellitus are the two major forms of diabetes. Type 2 diabetes mellitus accounts for more than 95% of the entire diabetic population. Incidence and prevalence of type 2 diabetes mellitus is increasing globally, especially in developing countries. Diabetes mellitus includes various complications associated with deterioration of function in the kidneys, retina, heart, and neurons. Complications associated with type 2 diabetes are risk factors for cardiovascular disease. Taking care of treatment cost, it is necessary to explore and understand the current therapeutic aspects of herbal medicinal plants for the prevention of diabetes. The current review summarizes updated information related to the most widely used medicinal plants used in the treatment and management of type 2 diabetes. Additionally, this review discusses promising results and challenges associated with herbal medicine. Herbal plants are a good alternative for patients with type 2 diabetes and remains unique sources for future drug discovery.

Objective To expore the functional changes of islet α- and β-cells in early-onset type 2 diabetes mellitus. Method Forty patients with early-onset type 2 diabetes mellitus (EOD group), 40 patients with late-onset type 2 diabetes mellitus (LOD group) and 30 normal controls (NC group) were recruited in this study and received oral glucose tolerance test, insulin and glucagon release tests. Blood glucose, insulin and glucagon levels were compared before and after glucose loading. Analysis of variance was used for comparison between groups, and t test or Mann-Whitney U test were used for pairwise comparison. Results There were no significant differences in blood glucose levels between EOD and LOD group at each time point (t=-1.101-0.007, both P>0.05); Fasting insulin and fasting glucagon in EOD group were significantly higher than those in LOD and control groups (U=140.000-218.000, both P<0.01); HOMA-IR in EOD group were higher than those in LOD and NC group (t=4.980, 2.094, both P<0.05), ISIMatsuda in EOD group were lower than those in LOD and NC group (t=-4.315, -2.146, both P<0.05), HOMA-β and ΔI30/ΔG30 in EOD group were higher than those in LOD group but lower than those in NC group (t=2.140-9.166, both P<0.05), AUCIns in EOD group were higher than those in LOD group (t=-1.527, 2.319, P<0.05), AUCGcg and Gcg/Glu in fasting and 1, 2 h after glucose loading in EOD group were higher than those in LOD group (2 h Gcg/Glu in EOD group was 1.4±0.7, and was 1.0±0.8 in LOD, t=2.113-3.354, both P<0.05). Conclusions β-cell function in EOD patients is better than that in LOD patients. However, compared with LOD patients, the insulin resistance and the islet α cell dysfunction are higher in EOD patients, including high levels of fasting glucagon, lower inhibition effect of blood glucose on glucagon, which may be one of the reasons for the early-onset type 2 diabetes mellitus. Key words: Diabetes mellitus, type 2; Early-onset; Islet α-cell; Islet β-cell

Objective To investigate the long-term outcome of postpartum glucose metabolism and predictive factors in patients with gestational diabetes mellitus (GDM). Methods A total of 1 191 patients diagnosed with GDM in the First Hospital of Peking University between November 2006 and October 2013, 320 (26.9%) patients were followed up and glucose metabolic data were collected during pregnancy, short-term postpartum (6-12 weeks) and long-term postpartum (1-6 years) periods. With type 2 diabetes mellitus (T2DM) as the end point event, the survival curve was drawn by Kaplan-Meier method to analyze the incidence of postpartum T2DM year by year, and Cox multivariate regression was used to analyze the predictive factors of postpartum T2DM. Results In 1-6 years of postpartum period, 9 (2.8%) cases had impaired fasting glucose (IFG), 71 (22.2%) had impaired glucose tolerance (IGT) and 14 (4.3%) had T2DM. Both of fasting plasma glucose (FPG) and 2 hour postprandial glucose (2hPG) elevated year by year in postpartum period. Kaplan-Meier survival curve indicated the cumulative incidence of T2DM were 0, 0.9%, 2.7%, 4.6%, 7.0% and 18.8% in 1-6 years of postpartum period, respectively. Early pregnancy weight, FPG/2hPG during pregnancy, FPG/2hPG/waist/hip ratio in early postpartum period were risk factors of long-term postpartum T2DM (all P<0.05). Body weight ≥72 kg in early pregnancy and FPG ≥5.2 mmol/L in early postpartum period were independent predictive factors, hazard ratio (HR) were 14.9 [95% confidence interval (CI) 2.3-96.1] and 18.2 (1.9-173.0) , respectively. Conclusions The cumulative incidence of T2DM in GDM patients increases annually, especially in the 5th-6th year of postpartum period. High body weight in early pregnancy and postpartum short-term FPG ≥5.2 mmol/L have important significance to predict the long-term outcome of postpartum glucose metabolism. Key words: Diabetes mellitus, gestational; Diabetes mellitus, type 2; Postpartum

Gestational diabetes mellitus (GDM) is one of the most common complications of pregnancy and the prevalence of GDM is increasing worldwide. Short- and long-term complications of GDM on mothers and fetuses are well-recognized. These include more than seven-fold higher risk for type 2 diabetes mellitus (T2DM) later in life in women with GDM than those without. Evidence supports that GDM shares several risk factors with T2DM, including genetic risks. This chapter reviewed studies on candidate genes shared by T2DM and GDM published from 1990 to 2011. At least 20 susceptible genes of T2DM have been studied in women with GDM in various races. Results from current association studies on T2DM susceptible genes in GDM have shown significant heterogeneity There may be primary evidence that polymorphisms of susceptible genes of T2DM such as transcription factor 7-like 2 (TCF7L2) gene, potassium channel voltage-gate KQT-like subfamily member 1 (KCNQ1) gene, and cyclin-dependent kinase 5 regulatory subunit-associated protein 1-like 1 (CDKAL1) gene, may increase risk of GDM. Associations between GDM and many genetic variants have led to different findings across populations. Many genetic polymorphisms related to GDM were investigated in a single study or a single population. Replication studies to verify contributions of both common and rare genetic variants for GDM and T2DM in specific racial/ethnic groups are needed.