Comparison of diagnostic accuracy and acceptability of self-sampling devices for human Papillomavirus detection: A systematic review.

Objective: Cervical cancer screening coverage remains low in many countries worldwide. Self-sampling approach for cervical cancer screening has a good potential to improve the screening coverage. This study aims to compare different types of HPV self-sampling devices for cervical cancer screening to identify the most accurate and acceptable device(s). Methods: A systematic review was performed on data extracted from all studies specific to HPV self-sampling devices by searching relevant articles in PubMed, Google Scholar, Scopus, Web of Science, ScienceDirect, Cochrane Library, and EBSCO published from 2013 to October 2023. The study was registered in PROSPERO (CRD42022375682). Results: Overall, 70 papers met the eligibility criteria for this systematic review and were included in the analysis: 22 studies reported self-sampling devices diagnostic accuracy, 32 studies reported self-sampling devices acceptability and 16 studies reported both (accuracy and acceptability). The most popular self-sampling devices were Evalyn Brush, FLOQ Swab, Cervex-Brush, and Delphi Screener. Out of overall 38 studies analyzing self-sampling devices' diagnostic accuracy, 94.7% of studies reported that self-collected specimens provided sensitivity and specificity comparable with clinician-collected samples; acceptability of Evalyn Brush, FLOQ Swab, Delphi Screener, and Colli-Pee, varied between 84.2% and 100%. Conclusion: The self-sampling approach has a good potential to increase cervical cancer screening coverage. Evalyn Brush, Cervex-Brush, FLOQ Swab, and Delphi Screener self-sampling devices for HPV detection were the most commonly utilized and found to be the most accurate, and patient-acceptable. HPV detection accuracy using these self-sampling devices had no significant difference compared to the sampling performed by healthcare providers.

Epidemiology of spontaneous pregnancy loss in Kazakhstan: A national population-based cohort analysis during 2014-2019 using the national electronic healthcare system.

INTRODUCTION: Spontaneous pregnancy loss (SPL) is a common health problem that affects 1:10 of childbearing women, and is linked with physical and psychological complications. As the number of nationwide studies on the incidence of SPL is few, especially from middle-income countries, in this study we investigated the epidemiology, complications and outcomes of SPL before 22 weeks of gestation by analyzing large-scale healthcare data from the Unified Nationwide Electronic Healthcare System (UNEHS) in Kazakhstan. MATERIAL AND METHODS: A population-based study among women who experienced SPL in any healthcare setting of the Republic of Kazakhstan during the period of 2014-2019. The International Classification of Diseases (ICD) 10th edition and ICD 9th edition's procedural codes were utilized to retrieve data using relevant diagnostic and procedural codes. RESULTS: In total, 207 317 records of women who have experienced an SPL before 22 weeks of gestation were analyzed from all Kazakhstani regions. The estimated prevalence of SPL was 8.7%, with a 20% decline over a 6-year period. The SPL cases ratio comprises on average 6.2 per 1000 reproductive-age women. Incomplete miscarriage (ICD-10 code "O03.4") was the most common type (37.8%), followed by blighted ovum (ICD-10 code "O02.0"; 34.1%) and missed abortion (ICD-10 code "O02.1"; 13.5%). The most common management methods were dilation and curettage of the uterus (ICD-9 code "69.0"; 84.7%) and aspiration curettage of the uterus (ICD-9 code "65.0"; 15%), whereas medical management was rarely performed (2.6%). CONCLUSION: The information available in UNEHS adequately identifies types of miscarriages and treatment methods. Although the prevalence of SPL before 22 weeks of gestation is decreasing, management of miscarriages requires closer attention.

Recurrent Pregnancy Loss Etiology, Risk Factors, Diagnosis, and Management. Fresh Look into a Full Box.

Recurrent pregnancy loss is a complex health challenge with no universally accepted definition. Inconsistency in definitions involves not only the number of spontaneous abortions (two or three) that are accepted for recurrent pregnancy loss but the types of pregnancy and gestational age at miscarriage. Due to the heterogeneity of definitions and criteria applied by international guidelines for recurrent pregnancy loss, the true incidence of recurrent miscarriage, which is reported to range from 1% to 5%, is difficult to estimate. Moreover, the exact etiology of recurrent pregnancy loss remains questionable; thus, it is considered a polyetiological and multifactorial condition with many modifiable and non-modifiable factors involved. Even after thoroughly evaluating recurrent pregnancy loss etiology and risk factors, up to 75% of cases remain unexplained. This review aimed to summarize and critically analyze accumulated knowledge on the etiology, risk factors, relevant diagnostic options, and management approach to recurrent pregnancy loss. The relevance of various factors and their proposed roles in recurrent pregnancy loss pathogenesis remains a matter of discussion. The diagnostic approach and the management largely depend on the etiology and risk factors taken into consideration by a healthcare professional as a cause of recurrent miscarriage for a particular woman or couple. Underestimation of social and health consequences of recurrent pregnancy loss leads to compromised reproductive health and psychological well-being of women after miscarriage. Studies on etiology and risk factors for recurrent pregnancy loss, especially idiopathic, should be continued. The existing international guidelines require updates to assist clinical practice.

Associations of Clusters of Cardiovascular Risk Factors with Insulin Resistance and Β-Cell Functioning in a Working-Age Diabetic-Free Population in Kazakhstan.

Cardiovascular risk factors aggregate in determined individuals. Patients with Type 2 diabetes mellitus (T2DM) have higher cardiovascular This study aimed to investigate insulinresistance (IR) and ß-cell function using the homeostasis model assessment (HOMA) indexes in a general Kazakh population and determine the effect he effect that cardiovascular factors may have on those indexes. We conducted a cross-sectional study among employees of the Khoja Akhmet Yassawi International Kazakh-Turkish University (Turkistan, Kazakhstan) aged between 27 and 69 years. Sociodemographic variables, anthropometric measurements (body mass, height, waist circumference, hip circumference), and blood pressure were obtained. Fasting blood samples were collected to measure insulin, glucose, total cholesterol (TC), triglycerides (TG), and high- (HDL) andlow-density lipoprotein (LDL) levels. Oral glucose tolerance tests were performed. Hierarchical and K-means cluster analyses were obtained. The final sample was composed of 427 participants. Spearmen correlation analysis showed that cardiovascular parameters were statistically associated with HOMA-ß (p < 0.001) and not with HOMA IR. Participants were aggregated into the three clusters where the cluster with a higher age and cardiovascular risk revealed deficient ß-cell functioning, but not IR (p < 0.000 and p = 0.982). Common and easy to obtain biochemical and anthropometric measurements capturing relevant cardiovascular risk factors have been demonstrated to be associated with significant deficiency in insulin secretion. Although further longitudinal studies of the incidence of T2DM are needed, this study highlights that cardiovascular profiling has a significant role not just for risk stratification of patients for cardiovascular prevention but also for targeted vigilant glucose monitoring.

Prophylactic Human Papillomavirus Vaccination: From the Origin to the Current State.

Immunization is the most successful method in preventing and controlling infectious diseases, which has helped saving millions of lives worldwide. The discovery of the human papillomavirus (HPV) infection being associated with a variety of benign conditions and cancers has driven the development of prophylactic HPV vaccines. Currently, four HPV vaccines are available on the pharmaceutical market: Cervarix, Gardasil, Gardasil-9, and the recently developed Cecolin. Multiple studies have proven the HPV vaccines' safety and efficacy in preventing HPV-related diseases. Since 2006, when the first HPV vaccine was approved, more than 100 World Health Organization member countries reported the implementation of HPV immunization. However, HPV vaccination dread, concerns about its safety, and associated adverse outcomes have a significant impact on the HPV vaccine implementation campaigns all over the world. Many developed countries have successfully implemented HPV immunization and achieved tremendous progress in preventing HPV-related conditions. However, there are still many countries worldwide which have not created, or have not yet implemented, HPV vaccination campaigns, or have failed due to deficient realization plans associated with establishing successful HPV vaccination programs. Lack of proper HPV information campaigns, negative media reflection, and numerous myths and fake information have led to HPV vaccine rejection in many states. Thus, context-specific health educational interventions on HPV vaccination safety, effectiveness, and benefits are important to increase the vaccines' acceptance for efficacious prevention of HPV-associated conditions.

Epidemiology of type 1 and type 2 diabetes mellitus in Kazakhstan: data from unified National Electronic Health System 2014-2019.

BACKGROUND: We aimed to explore descriptive epidemiology of T1 and T2 Diabetes Mellitus (DM) and to investigate demographic factors and comorbidities associated with all-cause mortality by aggregating and utilizing large-scale administrative healthcare data from the Unified National Electronic Health System (UNEHS) of Kazakhstan for 2014-2019 years period. METHODS: A total of 475,539 individuals were included in the analyses. The median years of follow-up for Type 1 DM patients accounted for 4.7 years and 4.5 years in Type 2 DM patients. We used Kaplan-Meier and log-rank test to calculate failure function and differences in survival by age, sex, ethnicity, and comorbidities with all-cause mortality for Type 1 and Type 2 DM. Cox proportional hazards regression analysis was used to obtain crude and adjusted hazard ratios. RESULTS: Prevalence of Type 1 and Type 2 DM increased 1.7 times from 2014 to 2019. Mortality of Type 1 and Type 2 DM also increased 4 times and 6 times from 2014 to 2019, respectively. Male sex, older age and Kazakh ethnicity were associated with a higher risk of all-cause death compared to females, younger age and other nationalities than Kazakh in patients with Type 1 and Type 2 DM. Coronary artery disease, diabetic nephropathy, stroke, amputations and neoplasms were associated with a higher risk of all-cause death. CONCLUSION: The prevalence and mortality rate of Type 1 and Type 2 DM increased during the years 2014-2019 in Kazakhstan. Male sex, older age and Kazakh ethnicity were associated with a higher risk of all-cause death compared to females, younger age and other nationalities than Kazakh. Coronary artery disease, diabetic nephropathy, stroke, amputations and neoplasms were associated with a higher risk of all-cause death.

ADIPOQ gene polymorphisms and haplotypes linked to altered susceptibility to PCOS: a case-control study.

RESEARCH QUESTION: What role do ADIPOQ variants play in controlling adiponectin concentrations and altered risk of polycystic ovary syndrome (PCOS)? DESIGN: Study subjects comprised 583 women with PCOS and 713 age-matched controls. Genotyping of rs182052, rs822393, rs822396, rs7649121, rs3774271, rs266729, rs3774261 and rs6773957 ADIPOQ polymorphisms was done by real-time polymerase chain reaction (PCR). RESULTS: Of the 16 ADIPOQ variants, the minor allele frequencies of rs182052, rs822393, rs822396, rs7649121, rs3774261 and rs6773957 were significantly different between PCOS cases and controls. Significant differences in rs266729 (P = 0.02), rs822396 (P = 0.02), rs3774261 (P < 0.001) and rs6773957 (P < 0.001) genotypes were also noted between PCOS cases and controls. Reduced PCOS risk was found with heterozygous rs266729, while increased risk was linked to heterozygous rs822396 and homozygous minor allele rs3774361, and in heterozygous and homozygous minor allele rs6773957 genotype carriers. Haplotype analysis identified two blocks based on linkage disequilibrium pattern; alleles coded as '1' (major) and '2' (minor). Within Block 1 (rs4632532, rs16861194, rs266729, rs182052, rs16861209, rs822393, rs822395, rs822396, rs7649121), haplotypes 111111111 and 212211221 were positively, while haplotypes 212212112 and 212211211 were negatively associated with PCOS. Within Block 2 (rs2241766, rs1501299, rs2241767, rs3774261, rs6773957, rs1063539) haplotypes 111221 and 112221 were positively, while haplotype 111111 was negatively associated with PCOS. CONCLUSIONS: This is the first study to confirm the association of rs182052, rs822393, rs7649121 and rs6773957 ADIPOQ variants with altered risk of PCOS. The varied association of ADIPOQ variants with PCOS in relation to earlier reports indicate there is an ethnic contribution to ADIPOQ association with PCOS.

Prevalence of Impaired Fasting Glucose and Type 2 Diabetes in Kazakhstan: Findings From Large Study.

Type 2 diabetes mellitus (T2DM) is a serious public health problem. A large proportion of patients with T2DM are unaware of their condition. People with undiagnosed T2DM are at a greater risk of developing complications, whereas prediabetes has an elevated risk of becoming T2DM. The aim of this study is to estimate the prevalence of impaired fasting glucose (IFG), undiagnosed and prior-diagnosed T2DM in Kazakhstan. A cross-sectional study was conducted in four geographically remote regions using the WHO STEP survey instrument. The status of T2DM of 4,753 participants was determined using the WHO diagnostic criteria based on fasting plasma glucose (FPG) level. As a result, the survey-weighted prevalence of IFG was 1.9% (95% CI 1.1%; 3.5%) and of T2DM was 8.0% (95% CI 3.8; 15.9). A total of 54% of T2DM have been newly diagnosed with T2DM. Being 55-64 years old (OR = 2.71, 95% CI 1.12; 6.60) and having lowered HDL-C level (OR = 3.72, 95% CI 1.68; 8.23) were found to be independent predictors for IFG. Being older than 45 years, a female (OR = 0.57, 95% CI 0.39; 0.83), having high waist circumference, was associated with newly diagnosed T2DM. Whereas, the age older than 45 years, high waist circumference, and family history of diabetes (OR = 2.42, 95% CI 1.64; 3.54) were associated with preexisting T2DM. This study shows a high prevalence of IFG and a high proportion of newly diagnosed T2DM in Kazakhstan. A series of risk factors identified in the study may be used to strengthen appropriate identification of IFG or undiagnosed patients in healthcare settings to deliver either preventive or therapeutic interventions aimed to reduce the incidence of T2DM or the delay of their complications. Further longitudinal studies are needed to confirm these associations in our population.

Seroprevalence and risk factors for hepatitis B and hepatitis C in three large regions of Kazakhstan.

BACKGROUND & AIMS: Kazakhstan has implemented comprehensive programs to reduce the incidence of Hepatitis B and Hepatitis C. This study aims to assess seroprevalence and risk factors for HBsAg and anti-HCV positivity in three large regions of Kazakhstan. METHODS: A cross-sectional study was conducted in three regions geographically remote from each other. Participants were randomly selected using a two-stage stratified cluster sampling and were surveyed by a questionnaire based on the WHO STEP survey instrument. Blood samples were collected for HBsAg and anti-HCV testing. RESULTS: A total of 4,620 participants were enrolled. The seroprevalence was 5.5% (95%CI: 3.6%-8.4%) for HBsAg and 5.1% (95%CI: 3.5%-7.5%) for anti-HCV antibodies. Both were more prevalent in the western and northern regions than in the southern. A history of blood transfusion was significantly associated with anti-HCV presence, with odds ratios (ORs) of 2.10 (95%CI: 1.37-3.21) and was borderline associated with HBsAg 1.39 (95%CI: 0.92-2.10), respectively. Having a family member with viral hepatitis was also borderline associated (2.09 (95%CI: 0.97-4.50)) with anti-HCV positivity. CONCLUSIONS: This study found a high-intermediate level of endemicity for HBsAg and a high level of endemicity for anti-HCV antibodies in three large regions of Kazakhstan. We found that history of surgery was not associated with HbsAg neither with anti-HCV seropositivity rates. Blood transfusion was associated with anti-HCV seropositivity, however, to investigate effectiveness of the introduced comprehensive preventive measures in health care settings, there is a need to conduct further epidemiological studies.

The Identification of Diabetes Mellitus Subtypes Applying Cluster Analysis Techniques: A Systematic Review.

Diabetes Mellitus is a chronic and lifelong disease that incurs a huge burden to healthcare systems. Its prevalence is on the rise worldwide. Diabetes is more complex than the classification of Type 1 and 2 may suggest. The purpose of this systematic review was to identify the research studies that tried to find new sub-groups of diabetes patients by using unsupervised learning methods. The search was conducted on Pubmed and Medline databases by two independent researchers. All time publications on cluster analysis of diabetes patients were selected and analysed. Among fourteen studies that were included in the final review, five studies found five identical clusters: Severe Autoimmune Diabetes; Severe Insulin-Deficient Diabetes; Severe Insulin-Resistant Diabetes; Mild Obesity-Related Diabetes; and Mild Age-Related Diabetes. In addition, two studies found the same clusters, except Severe Autoimmune Diabetes cluster. Results of other studies differed from one to another and were less consistent. Cluster analysis enabled finding non-classic heterogeneity in diabetes, but there is still a necessity to explore and validate the capabilities of cluster analysis in more diverse and wider populations.

A Low-Carbohydrate Diet Improves Glucose Metabolism in Lean Insulinopenic Akita Mice Along With Sodium-Glucose Cotransporter 2 Inhibitor.

Objective: A low-carbohydrate diet (LC) can be beneficial to obese subjects with type2 diabetes mellitus (T2DM). Sodium-glucose cotransporter 2 inhibitor (SGLT2i) presents prompt glucose-lowering effects in subjects with T2DM. We investigated how LC and SGLT2i could similarly or differently influence on the metabolic changes, including glucose, lipid, and ketone metabolism in lean insulinopenic Akita mice. We also examined the impacts of the combination. Methods: Male Akita mice were fed ad libitum normal-carbohydrate diet (NC) as a control or low-carbohydrate diet (LC) as an intervention for 8 weeks with or without SGLT2i treatment. Body weight and casual bold glucose levels were monitored during the study, in addition to measuring TG, NEFA, and ketone levels. We quantified gene expressions involved in gluconeogenesis, lipid metabolism and ketogenesis in the liver and the kidney. We also investigated the immunostaining analysis of pancreatic islets to assess the effect of islet protection. Results: Both LC and SGLT2i treatment reduced chronic hyperglycemia. Moreover, the combination therapy additionally ameliorated glycemic levels and preserved the islet morphology in part. LC but not SGLT2i increased body weight accompanied by epididymal fat accumulation. In contrast, SGLT2i, not LC potentiated four-fold ketone production with higher ketogenic gene expression, in comparison with the non-treated Akita mice. Besides, the combination did not enhance further ketone production compared to the SGLT2i alone. Conclusions: Our results indicated that both LC and SGLT2i reduced chronic hyperglycemia, and the combination presented synergistic favorable effects concomitantly with amelioration of islet morphology, while the combination did not enhance further ketosis in Akita mice.

Apolipoprotein E genetic polymorphism influence the susceptibility to nephropathy in type 2 diabetes patients.

BACKGROUND: An association between Apolipoprotein E (Apo E) alleles and genotypes and diabetic nephropathy (DN) was suggested, but with inconsistent results. We tested the relationship between serum lipids, Apo E alleles and genotypes with type 2 diabetes (T2DM), and DN pathogenesis. METHODS: Study subjects comprised 1389 normoglycemic controls, and 1422 T2DM patients, of whom 825 were normoalbuminuric (DWN), and 597 presented with nephropathy (DN). RESULTS: Significantly lower Apo ε2, and higher Apo ε4 allele frequencies was seen among T2DM patients than controls. Significantly higher frequency of ε3/ε4, and lower frequencies of ε3/ε3, ε2/ε3, and ε4/ε4 carriers was seen among T2DM cases. Apo ε2-carrying individuals were more frequently found in controls than in patients, while significantly higher frequency of ε4-carrying genotypes was seen in T2DM cases. Significantly higher ε2, and lower ε3 allele frequencies were noted for DN group compared to DWN group. Significantly higher frequency of ε2-containing ε2/ε3 and ε2/ε4, and lower frequencies of ε3/ε3 carriers was seen among DN cases. Apo ε3/ε3 was associated with higher total cholesterol, LDL-cholesterol, and triglyceride levels in DN patients, and significantly higher triglyceride levels were seen in ε2/ε3-carrying DN patients. Logistic regression analysis confirmed the association of Apo ε3-containing ε3/ε3, ε2/ε3, and ε3/ε4, and Apo ε2-containing ε2/ε4 with DN, after controlling for key covariates. CONCLUSION: The results of this case-control study provide evidence that the ε2 and ε3 alleles of APOE modify lipid profile, and constitute independent risk factors of DN in type 2 diabetes. The molecular mechanisms underlying this risk is discussed.

Sodium-Glucose Cotransporter 2 Inhibitor and a Low Carbohydrate Diet Affect Gluconeogenesis and Glycogen Content Differently in the Kidney and the Liver of Non-Diabetic Mice.

A low carbohydrate diet (LCHD) as well as sodium glucose cotransporter 2 inhibitors (SGLT2i) may reduce glucose utilization and improve metabolic disorders. However, it is not clear how different or similar the effects of LCHD and SGLT2i are on metabolic parameters such as insulin sensitivity, fat accumulation, and especially gluconeogenesis in the kidney and the liver. We conducted an 8-week study using non-diabetic mice, which were fed ad-libitum with LCHD or a normal carbohydrate diet (NCHD) and treated with/without the SGLT-2 inhibitor, ipragliflozin. We compared metabolic parameters, gene expression for transcripts related to glucose and fat metabolism, and glycogen content in the kidney and the liver among the groups. SGLT2i but not LCHD improved glucose excursion after an oral glucose load compared to NCHD, although all groups presented comparable non-fasted glycemia. Both the LCHD and SGLT2i treatments increased calorie-intake, whereas only the LCHD increased body weight compared to the NCHD, epididimal fat mass and developed insulin resistance. Gene expression of certain gluconeogenic enzymes was simultaneously upregulated in the kidney of SGLT2i treated group, as well as in the liver of the LCHD treated group. The SGLT2i treated groups showed markedly lower glycogen content in the liver, but induced glycogen accumulation in the kidney. We conclude that LCHD induces deleterious metabolic changes in the non-diabetic mice. Our results suggest that SGLT2i induced gluconeogenesis mainly in the kidney, whereas for LCHD it was predominantly in the liver.

High glucose induces platelet-derived growth factor-C via carbohydrate response element-binding protein in glomerular mesangial cells.

Persistent high concentration of glucose causes cellular stress and damage in diabetes via derangement of gene expressions. We previously reported high glucose activates hypoxia-inducible factor-1αand downstream gene expression in mesangial cells, leading to an extracellular matrix expansion in the glomeruli. A glucose-responsive transcription factor carbohydrate response element-binding protein (ChREBP) is a key mediator for such perturbation of gene regulation. To provide insight into glucose-mediated gene regulation in mesangial cells, we performed chromatin immunoprecipitation followed byDNAmicroarray analysis and identified platelet-derived growth factor-C (PDGF-C) as a novel target gene of ChREBP In streptozotocin-induced diabetic mice, glomerular cells showed a significant increase inPDGF-C expression; the ratio ofPDGF-C-positive cells to the total number glomerular cells demonstrated more than threefold increase when compared with control animals. In cultured human mesangial cells, high glucose enhanced expression ofPDGF-C protein by 1.9-fold. Knock-down of ChREBPabrogated this induction response. UpregulatedPDGF-C contributed to the production of typeIVand typeVIcollagen, possibly via an autocrine mechanism. Interestingly, urinaryPDGF-C levels in diabetic model mice were significantly elevated in a fashion similar to urinary albumin. Taken together, we hypothesize that a high glucose-mediated induction ofPDGF-C via ChREBPin mesangial cells contributes to the development of glomerular mesangial expansion in diabetes, which may provide a platform for novel predictive and therapeutic strategies for diabetic nephropathy.

Pancreatic glucose-dependent insulinotropic polypeptide (GIP) (1-30) expression is upregulated in diabetes and PEGylated GIP(1-30) can suppress the progression of low-dose-STZ-induced hyperglycaemia in mice.

AIMS/HYPOTHESIS: Glucose-dependent insulinotropic polypeptide (GIP) is a peptide hormone released from gut K cells. While the predominant form is GIP(1-42), a shorter form, GIP(1-30), is produced by pancreatic alpha cells and promotes insulin secretion in a paracrine manner. Here, we elucidated whether GIP(1-30) expression is modulated in mouse models of diabetes. We then investigated whether PEGylated GIP(1-30) can improve islet function and morphology as well as suppress the progression to hyperglycaemia in mice treated with low-dose streptozotocin (LD-STZ). METHODS: We examined pancreatic GIP immunoreactivity in rodent diabetic models. We synthesised [D-Ala(2)]GIP(1-30) and modified the C-terminus with polyethylene glycol (PEG) to produce a dipeptidyl peptidase-4 (DPP-4)-resistant long-acting GIP analogue, [D-Ala(2)]GIP(1-30)-PEG. We performed i.p.GTT and immunohistochemical analysis in non-diabetic and LD-STZ diabetic mice, with or without administration of [D-Ala(2)]GIP(1-30)-PEG. RESULTS: Pancreatic GIP expression was concomitantly enhanced with alpha cell expansion in rodent models of diabetes. Treatment with DPP-4 inhibitor decreased both the GIP- and glucagon-positive areas and preserved the insulin-positive area in LD-STZ diabetic mice. Body weight was not affected by [D-Ala(2)]GIP(1-30)-PEG in LD-STZ or non-diabetic mice. Treatment with GIP significantly ameliorated chronic hyperglycaemia and improved glucose excursions in LD-STZ mice. Treatment with GIP also reduced alpha cell expansion in the islets and suppressed plasma glucagon levels compared with non-treated LD-STZ mice. Additionally, [D-Ala(2)]GIP(1-30)-PEG preserved beta cell area via inhibition of apoptosis in LD-STZ mice. CONCLUSIONS/INTERPRETATION: Our data suggest that GIP(1-30) expression is upregulated in diabetes, and PEGylated GIP(1-30) can suppress the progression to STZ-induced hyperglycaemia by inhibiting beta cell apoptosis and alpha cell expansion.