Expert Opinion: Use of sodium glucose co-transporter type-2 inhibitors in South Asian population -The Pakistan perspective.

Sodium-glucose co-transporter type 2 inhibitors (SGLT 2- i)are increasingly being used in the management of type 2 diabetes mellitus (T2DM). With the novel insulinindependent glycosuric action, these agents help to attain glycaemic goals by lowering HbA1c and fasting blood glucose. In addition, these agents improve metabolic control in diabetes and ameliorate comorbidities like obesity and hyper tension. Beneficial effec ts on cardiovascular outcomes have been a key attraction for physicians. These agents are used alone or in combination with oral antidiabetic agents and insulin to attain glycaemic and metabolic targets. A major disadvantagewith these agents is the increased risk for genital andurinary infections. When used in appropriate settings, there is no additional increased risk of hypoglycaemia or volume depletion with these agents. Available evidence suggests good efficacy and safety of these agents in diabetes management. The easy and convenient oncedaily dosing should be customized according to patient needs and glycaemic profiles.

Cardiovascular disease risk factors in Pakistani population with newly diagnosed Type 2 diabetes mellitus: A cross-sectional study of selected family practitioner clinics in four provinces of Pakistan (CardiP Study).

OBJECTIVE: To explore cardiovascular risk factors in people with newly-diagnosed type 2 diabetes mellitus. METHODS: The cross-sectional, prospective, multicentre, study was conducted from June 2014 till July 2015 at family practice clinics in 27 cities across Pakistan, and comprised individuals aged 30-50 years diagnosed with type 2 diabetes mellitus within the preceding six months. Laboratory investigations were conducted at Shaukat Khanum Memorial Cancer Hospital and Research Centre, Lahore, and Aga Khan University Hospital, Karachi. The 10-year absolute risk of fatal or non-fatal coronary heart disease and stroke was calculated using the United Kingdom Prospective Diabetes Study Risk Engine version 2.0. Data were analysed using SPSS 19. RESULTS: Out of 888 subjects, 362(40.8%) were women and 526(59.2%) were men. The overall mean presenting age was 42.4}5.8 years. After stratification by age, those ≥40 years were significantly associated with higher glycated haemoglobin (p=0.02) and those ≤39 years were associated with higher levels of very low density lipoprotein (p=0.001) and triglyceride (p=0.006). The mean risk estimate for CHD was 9.7% (95% Confidence Interval (CI) 9.0- 10.1)), for fatal CHD 4.4% (95% CI 4.0-4.6), for stroke 1.5% (95% CI 1.2-1.7), and for fatal stroke 0.25% (95% CI 0.24- 0.26). CONCLUSIONS: There is a need for screening cardiovascular risk factors even in younger age groups of newlydiagnosed diabetes.

Lack of uniformity in screening, diagnosis and management of gestational diabetes mellitus among health practitioners across major cities of Pakistan.

OBJECTIVE: To determine knowledge, attitude and practice (KAP) regarding management of Gestational Diabetes Mellitus (GDM) among Health Care Providers in major cities of Pakistan. METHODS: A knowledge, attitude and practice (KAP) questionnaire based study was conducted in major cities in Pakistan from health care providers in public and private hospitals and clinics. Questionnaires were provided to the health care providers regarding screening, diagnosis and management of patients with GDM. Data analysis was done using IBM SPSS 20. RESULTS: A total of 210 doctors took part in the study. 55 (26%) reported using fasting blood glucose as screening test for GDM whereas 129(61.4%) respondents used Oral Glucose Tolerance based WHO criteria for diagnosing GDM. Thirty six (17%) and 98(46.7%) doctors referred their patients to Gynecologists. For treating GDM, 64(30.5%) doctors prescribed insulin (NPH/Regular, 70/30 Mix). 112 (53.5) doctors used combination of capillary glucose by glucometer and plasma blood glucose tests for monitoring of glycemic control of patients with GDM. CONCLUSION: There is lack of agreed screening tests and criteria for diagnosis and management of GDM patients. Doctors need to be educated to follow evidence based diagnostic and management guidelines so that GDM patients can be effectively managed. Recently released South Asian Federation Societies and Pakistan Endocrine Society guidelines could be much needed consensus guidelines for doctors to apply in their daily practice to improve GDM diagnosis and treatment.

A simple integrated primary health care based model for detection of diabetic retinopathy in resource-limited settings in Pakistani population.

OBJECTIVE: To find out prevalence of Diabetic Retinopathy in general population of three districts in Pakistan. METHODS: A community based cross-sectional survey was conducted in three large districts of Pakistan namely Rawalpindi in Punjab, Peshawar in Khyber Pakhtoonkhwa and Hyderabad in Sindh between January 2013 and August 2015. Lady Health Workers identified individuals at high risk for diabetes based on pre-defined criteria. High risk population was tested for dysglycemia. Fundoscopic evaluation for evidence of DR was performed in all individuals with a random blood glucose >190mg/dl. Individuals with the evidence of DR were referred to affiliated tertiary care ophthalmology departments. RESULTS: A total of 42,629 individuals reported at the project sites and 63% (n=26,859) were female. Fifty one percent (n=21,989) individuals met high risk criteria. Out of these 21,989 individuals, dysglycemia was found in 3,869 (17.6%). Fundoscopy showed evidence of DR in 1,042 (27%) individuals. Amongst high risk population, dysglycemia was significantly more common in females as compared to males. The frequency of DR in dysglycemic patients was comparable across both gender groups. CONCLUSION: The prevalence of DR in Pakistani population is alarmingly high. This preventable cause of blindness is largely undiagnosed in our population and a simple integrated model based on primary health care facilities can help identify and treat a large population of DR patients.

Causes of short stature in Pakistani children found at an Endocrine Center.

BACKGROUND AND OBJECTIVE: Short stature is defined as height below 3rd centile. Causes of short stature can range from familial, endocrine disorders, chronic diseases to chromosomal disorders. Most common cause in literature being idiopathic short stature. Early detection and management of remedial disorders like malnutrition and vitamin D deficiency, Endocrine disorders like growth hormone deficiency & hypothyroidism can lead to attainment of expected height. Pakistani data shows idiopathic short stature as the most common cause of short stature. Our study aimed at detecting causes of short stature in children/adolescents at an Endocrine referral center. METHODS: A retrospective study was conducted at WILCARE Center for Diabetes, Endocrinology & Metabolism, Lahore on 70 well-nourished children/adolescents. The patients had been evaluated clinically, biochemically and radiologically as needed. Biochemical testing included hormonal testing as well to detect endocrine causes. Data was entered and analyzed in SPSS 20.0. RESULTS: Leading cause of short stature in our population was Growth Hormone (GH) deficiency seen in 48 out of 70 (69%) patients. Second most common endocrine abnormality seen in these patients was Vitamin D deficiency [44 out of 70 patients (63%)]. Primary hypothyroidism; pan-hypopituitarism & adrenal insufficiency were other endocrine causes. The weight for age was below 3rd percentile in 57 (81%) patients, with no association with other major causes. CONCLUSION: Growth hormone and Vitamin D deficiency constitute one of the major causes of short stature among well-nourished children with short stature in Pakistan.

Expanded dengue syndrome: subacute thyroiditis and intracerebral hemorrhage.

BACKGROUND: Although most symptomatic dengue infections follow an uncomplicated course, complications and unusual manifestations are increasingly being reported due to rising disease burden. Expanded dengue syndrome is a new entity added into World Health Organization (WHO) classification system to incorporate this wide spectrum of unusual manifestations. We report a case of expanded dengue syndrome with subacute thyroiditis and intracerebral hemorrhage. This is the first case report of thyroiditis in dengue infection. CASE PRESENTATION: A 20 years old man presented with fever, myalgias, arthralgias, retro-orbital pain, vomiting and gum bleeding during a large dengue outbreak in Lahore, Pakistan. On 7th day of illness patient became afebrile, but he developed severe headaches, unconsciousness followed by altered behavior. On 9th day of illness patient developed painful neck swelling accompanied by fever, tremors, palpitations, hoarseness of voice and odynophagia. Examination revealed acutely swollen, tender thyroid gland along with features of hyperthyroidism. Laboratory evaluation revealed stable hematocrit, thrombocytopenia and leukopenia. Patient had seroconverted for anti-dengue IgM antibodies on the 10th day of illness. A non-contrast Computed Tomogram (CT) of the brain showed right frontal lobe hematoma. Thyroid profile showed increased free T3 and T4 and low TSH. Technetium thyroid scan showed reduced tracer uptake. He was diagnosed as having subacute thyroiditis and treated with oral prednisolone and propranolol. Follow up CT brain showed resolving hematoma. Patient's recovery was uneventful. CONCLUSION: Subacute thyroiditis may develop during the course of dengue fever and should be included as a manifestation of expanded dengue syndrome. It should be suspected in patients with dengue fever who develop painful thyroid swelling and clinical features of hyperthyroidism.

Compliance with hygiene practices among healthcare workers at an academic hospital emergency department.

INTRODUCTION: Healthcare-associated infections (HCAIs) are an important contributor to patient morbidity and mortality. Healthcare workers (HCWs) hands are the chief mode of transmission of HCAIs. The emergency centre (EC) is frequently the first point of contact for patients within the health care system. The aim of this study is to determine compliance with hygiene practices among healthcare workers at a tertiary hospital EC. METHODS: Hygiene practices of staff were observed over a six-week period. Data pertaining to compliance rates with hand cleansing and other hygiene practices was collected. Consent was obtained retrospectively to avoid influencing participant behaviour. RESULTS: From a total of 477 potential hygiene opportunities, compliance with hand hygiene was only 34.4% (n = 164). Hand cleansing with an alcohol-based hand rub was observed in 87 (26.7%) of the 326 (68.3%) opportunities where it was indicated, while handwashing with soap and water was observed in 35 (23.2%) of the 151 opportunities where this was indicated. Compliance to each of the six steps of handwashing ranged between 62.2% and 83.5%, with there being a gradual deterioration in compliance from step one through to step six. Compliance with 'bare below the elbows' was observed in 242 (50.7%) opportunities while disposable surgical gloves were worn on 85 (44.7%) of the 190 opportunities where this was indicated. CONCLUSION: Compliance with hygiene practices among EC HCWs is suboptimal. Various strategies including ongoing systematic training and regular audits may improve overall hygiene practices among EC staff.

A Comparative Assessment of the Nova Stat Profile Prime Plus® Critical Care Analyzer.

BACKGROUND: Point-of-care testing (POCT) plays an integral role in the management of acutely ill patients presenting to the emergency department (ED). Due to its rapid turnaround time, POCT has been shown to improve ED workflow, reduce unnecessary admissions and lessen the burden on ED staff. The aim of the study was to compare the accuracy, precision and linearity of the Nova Stat Profile Prime Plus® (Nova Biomedical, Waltham, MA, USA) to the Radiometer ABL800 FLEX® (Radiometer South Africa Pty Ltd, Gauteng) and the Abbott i-stat Chem8+® (Abbott, Princeton, NJ, USA) POCT analyzers. METHODS: A convenience sample of 150 discarded whole blood specimens was obtained and analyzed. Paired test measurements were conducted for method comparison. Accuracy was measured by pairing individual results from the Nova Stat Profile Prime Plus® with either the Radiometer ABL800 FLEX® or the Abbot i-stat Chem8+® analyzers by calculating the differences. RESULTS: The with-in run percentage coefficient of variation (%CV) was below 2.4% for pH, carboxyhemoglobin (COHb), deoxyhemoglobin (HHb), total hemoglobin (tHb), total bilirubin (tBil), sodium (Na), potassium (K), chloride (Cl), ionized calcium (iCa), urea, glucose and lactate, and was below 5.1% for all other analytes. The day-to-day %CV was below 1.6% for pH, COHb, HHb, tHb, tBil, Na, K, Cl, iCa, urea, glucose and lactate, and below 6.10% for all other analytes. The correlation coefficient (r) was 0.351 and ranged from 0.897 to 0.998 for all analytes. The mean bias was minimal for all analytes. CONCLUSION: There was a good correlation between the Nova Stat Profile Prime Plus® and the Radiometer ABL800 FLEX®/Abbott i-STAT Chem8+® POCT analyzers. The Stat Profile Prime Plus® exhibited good precision both within-run and day-to-day.

Type 2 diabetes prevalence in Pakistan: what is driving this? Clues from subgroup analysis of normal weight individuals in diabetes prevalence survey of Pakistan.

BACKGROUND: Type 2 diabetes mellitus (T2DM) is a global health tissue. We determined factors relating to the likelihood of developing T2DM in normal BMI individuals. METHODOLOGY: This was a cross-sectional community-based representative survey, of people aged ≥20 years in Pakistan, using HBA1c as the screening tool. The prevalence of T2DM/prediabetes in people having normal BMI together with associated risk factors was estimated. RESULTS: Of 6824 normal BMI individuals, there was still a high prevalence of T2DM 14.92% and in underweight at 10.14% (overall prevalence 16.96%). Corresponding rates for prediabetes for the normal BMI category: 9.79% and underweight 8.99%. Multivariate logistic regression modeling for normal BMI individuals, showed a significantly increased risk of T2DM with increasing age (odds ratio [OR] 2.1, 3.3, 4.5 and 4.8, P < 0.001 for 31-40, 41-50, 51-60 and 61 years and above respectively, compared to age decade 20-30 years). Similarly, there was a significantly high risk of T2DM with lower education level [OR for no vs graduate 2.4, 95% confidence interval (CI) 1.5-3.8]. There was a significantly increased risk of T2DM in individuals having a positive family history [OR 4.3 (95% CI 7.0-11.5)]. Overall the influence of overweight/obese on T2DM occurrence (20% increased risk) was much less than in other regions of the world. CONCLUSION: There are higher than expected rates of T2DM/prediabetes in Pakistani ethnicity normal BMI individuals. Targeted screening of older individuals with historical lack of educational opportunity, with a family history of T2DM even if of normal BMI may result in a significant benefit in the Pakistan population.

Diabetes Prevalence Survey of Pakistan (DPS-PAK): prevalence of type 2 diabetes mellitus and prediabetes using HbA1c: a population-based survey from Pakistan.

OBJECTIVES: We conducted a Pakistan-wide community-based survey on the prevalence of type 2 diabetes using glycated haemoglobin (HbA1c) as the screening test. The aim was to estimate diabetes prevalence across different demographic groups as well as all regions of Pakistan. DESIGN, SETTINGS AND PARTICIPANTS: Multistaged stratified cluster sampling was used for the representative selection of people aged ≥20 years, residing in 378 sampled clusters of 16 randomly selected districts, in this cross-sectional study. Eligible participants had blood drawn for HbA1c analyses at field clinics near to their homes. The oral glucose tolerance test (OGTT) was conducted on a subsample of the participants. Overall and stratified prevalence of type 2 diabetes and its association with risk factors were estimated using logistic regression models. MAIN OUTCOME MEASURES: Prevalence of prediabetes and type 2 diabetes. RESULTS: Of 18 856 eligible participants the prevalence of prediabetes was 10.91% (95% CI 10.46 to 11.36, n=2057) and type 2 diabetes was 16.98% (95% CI 16.44 to 17.51, n=3201). Overall, the mean HbA1c level was 5.62% (SD 1.96), and among newly diagnosed was 8.56% (SD 2.08). The prevalence was highest in age 51-60 years (26.03%, p<0.001), no formal education (17.66%, p<0.001), class III obese (35.09%, p<0.001), family history (31.29%, p<0.001) and female (17.80%, p=0.009). On multivariate analysis, there was a significant association between type 2 diabetes and older age, increase in body mass index and central obesity, positive family history, and having hypertension and an inverse relation with education as a categorical variable. On a subsample (n=1027), summary statistics for diagnosis of diabetes on HbA1c showed a sensitivity of 84.7%, specificity of 87.2% and area under the receiver operating characteristic curve 0.86, compared with OGTT. CONCLUSIONS: The prevalence of type 2 diabetes and prediabetes is much higher than previously thought in Pakistan. Comprehensive strategies need to be developed to incorporate screening, prevention and treatment of type 2 diabetes at a community level.

Cardiovascular Autonomic Neuropathy and its Association with Cardiovascular and All-cause Mortality in Patients with End-stage Renal Disease.

Background End-stage renal disease frequently leads to increased cardiovascular mortality. Cardiovascular autonomic neuropathy (CAN) may be predictive of cardiac arrhythmias and sudden cardiac death in patients with end-stage renal disease. Methods A total of 70 patients with end-stage renal disease were included in the study. The assessment of cardiac dysautonomia was based on the four standardized tests performed at the baseline and, again, at the end of the study. The criteria for CAN included at least two abnormal test results. Results Fifty of 70 patients completed the study and were followed-up after one year. Out of the 50 patients, 44 (88%) had CAN at baseline. Twelve (24%) patients died at the one-year follow-up. Sudden cardiac death was reported in seven out of 12 (58%) patients. All seven patients who died had high dysautonomia scores (three abnormal tests) at the baseline. There was a significantly higher percentage of patients with all four abnormal tests amongst patients who died of any cause (56% vs. 17%; RR 6.07, 95% CI 1.29-28.49; p-value 0.02) or due to sudden cardiac death (43% vs. 10.5%; RR 6.37, 95% CI 1.03-39.36; p-value 0.04). All five patients who did not have CAN at the baseline developed this abnormality on repeat testing after one year. Conclusion The prevalence of CAN in patients with end-stage renal disease on maintenance hemodialysis was significantly higher. CAN was an independent predictor of all-cause and cardiovascular mortality, which highlights it as a risk stratification tool in patients with end-stage renal disease.

The Bhubaneswar Declaration on Sports Endocrinology, 2018.

Sports and endocrinology are complex interrelated disciplines. Sports and exercise modulate endocrine and metabolic health, and are used to prevent and manage disease. Endocrine and metabolic function influence participation and performance in sports activity. The Bhubaneswar Declaration, released on the occasion of the Endocrine Society of India Conference, resolves to promote the science of sports endocrinology. The authors commit to optimize endocrine health in sports persons, encourage safe use of sports to promote health, and prevent misuse of endocrine interventions in sports.

Consensus Recommendations on Sulfonylurea and Sulfonylurea Combinations in the Management of Type 2 Diabetes Mellitus - International Task Force.

For decades, sulfonylureas (SUs) have been important drugs in the antidiabetic therapeutic armamentarium. They have been used as monotherapy as well as combination therapy. Focus on newer drugs and concerns about the risk of severe hypoglycemia and weight gain with some SUs have led to discussion on their safety and utility. It has to be borne in mind that the adverse events associated with SUs should not be ascribed to the whole class, as many modern SUs, such as glimepiride and gliclazide modified release, are associated with better safety profiles. Furthermore, individualization of treatment, using SUs in combination with other drugs, backed with careful monitoring and patient education, ensures maximum benefits with minimal side effects. The current guidelines, developed by experts from Africa, Asia, and the Middle East, promote the safe and smart use of SUs in combination with other glucose-lowering drugs.

Cardiovascular effects of insulin sensitizers in diabetes.

Diabetic patients have a greatly increased relative risk of cardiovascular disease compared with patients without diabetes. Type 2 diabetes is caused by a combination of insulin resistance and impaired pancreatic secretion. Thiazolidinediones are a relatively new class of compounds for the treatment of type 2 diabetes mellitus that lower glucose levels by decreasing insulin resistance and glucose production by the liver. The cardiovascular benefits of thiazolidinediones include an increase in high-density lipoprotein, reduction in blood pressure, improvement in endothelial function, attenuation of markers of inflammation and reduction in albuminuria. Ongoing clinical trials are underway investigating the role of thiazolidinediones in the prevention of type 2 diabetes mellitus.

Potential cardiovascular benefits of insulin sensitizers.

A multiple risk factor approach is needed in patients who have type 2 diabetes. Because many risk factors are linked with IR, treatment with insulin sensitizers has the potential to modulate these risk factors favorably. TZDs 'have many important effects beyond lowering blood glucose. By targeting IR, they improve many cardiovascular risk factors that are associated with the IR syndrome. In particular, they increase HDL-C, have anti-inflammatory effects, improve endothelial function and fibrinolysis, and decrease carotid intimal thickness; however, no evidence-based studies on cardiovascular outcomes are available to substantiate the potential cardioprotective effects of TZDs. Several clinical trials that were designed to investigate the effect that these agents have on reducing cardiovascular events are well under way.

Endothelial and erectile dysfunction, diabetes mellitus, and the metabolic syndrome: common pathways and treatments?

The past decade has witnessed a dramatic increase in the prevalence of obesity. Comorbidities of obesity include type 2 diabetes mellitus, hypertension, and lipid abnormalities, all of which contribute to cardiovascular disease (CVD) and are associated with endothelial dysfunction. These abnormalities frequently cluster in individuals, and the term metabolic syndrome is now widely used to define this cluster. The syndrome is frequently (although not invariably) associated with insulin resistance and CVD. Diabetes is associated with CVD, which may be asymptomatic in some cases, particularly when associated with autonomic neuropathy. This has implications for guidelines on the evaluation of patients with erectile dysfunction (ED) and CVD. Treatment of ED in men with diabetes has been revolutionized by the introduction of phosphodiesterase 5 inhibitors. However, men with diabetes tend to respond less positively to these agents, at least as currently prescribed. This decreased responsiveness may be related to the severity of endothelial function in patients with diabetes. Additional therapeutic strategies may be needed to overcome this problem.

Role of insulin secretagogues and insulin sensitizing agents in the prevention of cardiovascular disease in patients who have diabetes.

In the absence of clinical trial evidence to compare the secretagogues with sensitizers, it is difficult to make recommendations about which class of drug is more important to prescribe for the prevention of cardiovascular disease in diabetes mellitus. Epidemiologic data supports insulin resistance as a major factor in cardiovascular disease through a variety of mechanisms. Because sensitizers improve insulin sensitivity and correct many of the vascular abnormalities that are associated with insulin resistance, it is tempting to suggest that they may be superior for this purpose. Conversely, meeting the goals that are recommended for glycemia also are important and achieving them may not be always possible with sensitizers, particularly in the later stages of the disease when insulin levels are not high,despite insulin resistance. In such situations,combination therapy may be needed with both types of drugs. No data are available on the cardiovascular effects of such combinations;some retrospective data suggest a possibility of increased events with the combination of sulfonylureas and metformin. Thus, further prospective studies in this area are necessary.

Turmeric use is associated with reduced goitrogenesis: Thyroid disorder prevalence in Pakistan (THYPAK) study.

INTRODUCTION: South Asian population has a particularly high prevalence of thyroid disorders mainly due to iodine deficiency and goitrogen use. There is no data available for prevalence of thyroid disorders in the general population living in nonmountainous regions of Pakistan. MATERIALS AND METHODS: A total of 2335 residents of Pak Pattan, Punjab, Pakistan were interviewed about demographic, dietary, medical and environmental history as well as screened for goiter. Individuals of all ages and either gender were included. RESULTS: Median age was 34 (10-88) years and 1164 (49.9%) were males. Median monthly income was 49 (3.9-137) USD. Six hundred and sixty-nine (28.7%) subjects had palpable goiter. 77.5% (n = 462) and 22.5% (n = 133) had World Health Organization Grade I and Grade II goiters respectively, further screened by measuring thyroid-stimulating hormone (TSH). In subjects with TSH <0.4 mg/dL, free T3 and free T4 levels were measured. In 185 goiter subjects when TSH was measured, 50% (n = 93) were euthyroid, 48% (n = 89) were hyperthyroid, and one subject each was hypothyroid and subclinically hyperthyroid. 29/89 hyperthyroid subjects underwent radionuclide scanning. Twelve subjects had heterogeneous uptake consistent with multinodular goiter, 12 subjects had diffuse uptake, two had cold nodules and two had hyperfunctioning single nodules. Goiter was significantly more common among females, unmarried individuals and individuals drinking tube well (subterranean) water. Goiter was less common among those who consumed daily milk, daily ghee (hydrogenated oil), spices, chilies, and turmeric. DISCUSSION: In our study population, goiter was endemic with very high prevalence of hyperthyroidism. Turmeric use was association with reduced goitrogenesis. Further studies to assess iodine sufficiency, thiocyanate exposure and autoimmunity need to be conducted. Masses consuming high goitrogen diets should be educated to incorporate turmeric, spices and green chilies in their cooking recipes, to reduce the risk of goiter development. In addition, use of iodized salt in their daily diet cannot be overemphasized.

Effects of peptides, with emphasis on feeding, pain, and behavior A 5-year (1999-2003) review of publications in Peptides.

Novel effects of naturally occurring peptides are continuing to be discovered, and their mechanisms of actions as well as interactions with other substances, organs, and systems have been elucidated. Synthetic analogs may have actions similar or antagonistic to the endogenous peptides, and both the native peptides and analogs have potential as drugs or drug targets. The journal Peptides publishes many leading articles on the structure-activity relationship of peptides as well as outstanding reviews on some families of peptides. Complementary to the reviews, here we extract information from the original papers published during the past five years in Peptides (1999-2003) to summarize the effects of different classes of peptides, their modulation by other chemicals and various pathophysiological states, and the mechanisms by which the effects are exerted. Special attention is given to peptides related to feeding, pain, and other behaviors. By presenting in condensed form the effects of peptides which are essential for systems biology, we hope that this summary of existing knowledge will encourage additional novel research to be presented in Peptides.

Diabetic nephropathy and retinopathy.

Diabetic nephropathy and retinopathy are arguably the two most dreaded complications of diabetes. Together they contribute to serious morbidity and mortality. As they progress to end-stage renal disease and blindness, they impose enormous medical, economic,and social costs on both the patient and the health care system. Because nephropathy and retinopathy are frequently linked in patients,this article reviews their common and individual aspects of pathophysiology, clinical features, and management.