Pathophysiological significance in abdominal fat distribution in non-obese children with type 2 diabetes.

The aim of the study was to determine the pathogenesis of non-obese children with type 2 diabetes, and its relationship with fat distribution. The study participants included 36 obese children with type 2 diabetes (age: 13.5 years, BMI: 28.3, BMI percentile: 91.9) and 30 non-obese children with type 2 diabetes (age: 13.5 years, BMI: 23.1, BMI percentile: 74.0). The proportion of female participants was significantly higher in non-obese children than in obese children (73.3% vs. 41.7%, p < 0.001). Abdominal fat distribution, evaluated by subcutaneous fat (SF) area, visceral fat (VF) area, and the ratio of VF area to SF area (V/S ratio), measured using computed tomography, and serum lipid levels and liver function were compared between the two groups. Non-obese children with type 2 diabetes had significantly smaller SF area and also smaller VF area than obese children with type 2 diabetes (SF area: 158.3 m2 vs. 295.3 m2, p < 0.001, VF area: 71.0 m2 vs. 94.7 m2, p = 0.032). Whereas non-obese children with type 2 diabetes had significantly greater V/S ratio than obese children with type 2 diabetes (0.41 vs. 0.31, p = 0.007).The prevalence of dyslipidemia and liver dysfunction were similar in the two groups. In conclusion, non-obese children with type 2 diabetes had excess accumulation of VF despite a small amount of SF, which might be associated with glucose intolerance and other metabolic disorders.

Difference in the early clinical course between children with type 1 diabetes having a single antibody and those having multiple antibodies against pancreatic ß-cells.

Islet-cell associated antibodies are predictive and diagnostic markers for type 1 diabetes. We studied the differences in the early clinical course of children with type 1 diabetes with a single antibody and those with multiple antibodies against pancreatic ß-cells. Sixty-seven children with type 1 diabetes aged less than 15 years diagnosed between 2010 and 2021 were included in the study and subdivided into two subgroups: children who were single positive for either glutamic acid decarboxylase (GAD) antibodies (n = 16) or insulinoma-associated antigen-2 (IA-2) antibodies (n = 13) and those positive for both antibodies (n = 38) at diagnosis. We compared the patients' clinical characteristics, pancreatic ß-cell function, and glycemic control during the 5 years after diagnosis. All clinical characteristics at diagnosis were similar between the two groups. One and two years after diagnosis, children who tested positive for both antibodies showed significantly lower postprandial serum C-peptide (CPR) levels than those who tested positive for either GAD or IA-2 antibodies (p < 0.05). In other periods, there was no significant difference in CPR levels between the two groups. There was a significant improvement in glycosylated hemoglobin (HbA1c) levels after starting insulin treatment in both groups (p < 0.05), but no significant difference in HbA1c levels between the groups. Residual endogenous insulin secretion may be predicted based on the number of positive islet-cell associated antibodies at diagnosis. Although there are differences in serum CPR levels, optimal glycemic control can be achieved by individualized appropriate insulin treatment, even in children with type 1 diabetes.

Association between scanning frequency of flash glucose monitoring and continuous glucose monitoring-derived glycemic makers in children and adolescents with type 1 diabetes.

BACKGROUND: We assessed the association between scanning frequency of flash glucose monitoring (FGM) and continuous glucose monitoring (CGM)-derived glycemic markers in children and adolescents with type 1 diabetes. METHODS: Subjects consisted of 85 children and adolescents with type 1 diabetes using FGM. We assessed the association between scanning frequencies of FGM- and CGM-derived metrics: Time in range (TIR) (70-180 mg/dL), time below range (TBR) (<70 mg/dL), time above range (>180 mg/dL), and other glycemic markers - laboratory-measured HbA1c and CGM-estimated glucose and HbA1c (eA1c) levels in the subjects. RESULTS: The mean number of scans was 11.5 ± 3.5 (5-20) times per day, and scanning was most frequently conducted during a period of 18-24 h. Scanning frequency showed significant positive correlation with TIR (r = 0.719, P < 0.0001) and inverse correlation with time above range (r = -0.743, P < 0.0001), but did not correlate with TBR. There were also significant inverse correlations between scanning frequency and glucose, HbA1c, and eA1c levels (r = -0.765, -0.815, and -0.793, respectively, P < 0.0001). CONCLUSIONS: Frequent glucose testing with FGM decreased hyperglycemia with increased TIR, but did not reduce TBR. Coping with a rapid fall of glucose and unexpected hypoglycemia with more advanced technology might contribute to a reduction in TBR.

Individualization of recommendations from the international consensus on continuous glucose monitoring-derived metrics in Japanese children and adolescents with type 1 diabetes.

We assessed the significance of recommendations from the international consensus on continuous glucose monitoring (CGM)-derived metrics in Japanese children and adolescents with type 1 diabetes. Eighty-five patients (age, 13.5 ± 4.7 years) who wore the FreeStyle® Libre for a 28-day period were enrolled in this study. Seventy-three patients were treated with multiple daily injections of insulin and 12 with insulin pump therapy without using a sensor-augmented pump or a predictive low-glucose suspend-function pump. We evaluated the relationship between CGM-derived metrics: time in range (TIR: 70-180 mg/dL), time below range (TBR: <70 mg/dL), and time above range (TAR: >180 mg/dL), and laboratory-measured HbA1c and estimated HbA1c (eA1c) levels calculated from the mean glucose values. The TIR was 50.7 ± 12.2% (23-75%), TBR was 11.8 ± 5.8% (2-27%), and TAR was 37.5 ± 13.5% (9-69%). The TIR was highly correlated with HbA1c level, eA1c level, and TAR, but not with TBR. An HbA1c level of 7.0% corresponded to a TIR of 55.1% (95% CI: 53.7-56.5%), whereas a TIR of 70% corresponded to an HbA1c level of 6.1% (95% CI: 5.9-6.3%). The results of eA1c levels were similar to those observed for HbA1c levels. From these findings, we conclude that low rates of a recommended TIR of 70% may be due to less use of advanced technology and insufficient comprehensive diabetes care. Ethnic characteristics including lifestyle and eating customs may have contributed to the result. CGM-derived targets must be individualized based on ethnic characteristics, insulin treatment and diabetes care, and needs of individuals with diabetes.

Economic Impact of Diabetes in Japan.

PURPOSE OF REVIEW: The economic burden of diabetes in Japan is already serious and will become greater in the future. We review the economic impact of diabetes in Japan to examine viable options for mitigating its effects. RECENT FINDINGS: Medical costs for diabetes have been increasing by US $1 million annually, reaching US $11 million in 2009, of which US $7 million was accounted for by people aged 65 years or older. The quality of treatment of diabetes in Japan is higher than in other regions in the world. This can be more effective for achieving glycemic control, but is also more expensive compared with conventional treatment. Because of the high cost of diabetes in Japan, a coordinated response is needed. Intervention trials for people with prediabetes aimed at preventing the occurrence of diabetes seem to be the most cost-effective method for lowering the medical costs of diabetes, rather than the use of new, expensive antidiabetic drugs in patients with established diabetes.

Changes in annual incidence of school children with type 2 diabetes in the Tokyo Metropolitan Area during 1975-2015.

OBJECTIVE: To analyze changes in the annual incidence of school students with type 2 diabetes detected by urine glucose screening at schools in the Tokyo Metropolitan Area during 1975-2015. METHODS: Trend in temporal changes in the annual incidence rate were analyzed using a joinpoint regression model and the joinpoints. Annual percent change (APC) was calculated for each segmented line regression. Average annual percent change (AAPC) was also calculated for the whole period analyzed. RESULTS: In total, 301 students, including 64 primary school students and 237 junior high school students, were diagnosed with type 2 diabetes. The overall incidence of type 2 diabetes (per 100 000/year) during the entire study period was 2.58 in all students, 0.80 in primary school students, and 6.41 in junior high school students. AAPC during the entire study period was estimated at -1.5 (not significant), and the incidence significantly increased during 1975-1982 (APC = 17.49, P < 0.05), but tended to decrease during 1982-2015 (APC = -1.01). In primary school students, the incidence significantly increased during1975-2010 (APC = 3.30, P < 0.05), and tended to decrease during 2010-2015 (APC = -29.61). In junior high school students, the incidence did not significantly change during the entire study period (APC = 0.06). CONCLUSIONS: We found increasing trend in the overall incidence of school students with type 2 diabetes during 1975-1982, but a decreased tendency in recent years. This could be due to changes observed during the same time period in the primary school students. Lifestyle changes might contribute to improved incidence of childhood type 2 diabetes.

Efficacy and safety of switching from insulin glargine to insulin degludec in young people with type 1 diabetes.

We evaluated the efficacy and safety of switching to insulin degludec (IDeg) from insulin glargine (IGlar) as basal-bolus therapy in young people with type 1 diabetes. The subjects were 36 patients, 21.3±1.0 years of age, with type 1 diabetes. IGlar had previously been injected once daily in 25 patients and twice daily in 11. They were then switched from IGlar to once-daily injection of IDeg. Both fasting plasma glucose (FPG) and HbA1c levels decreased significantly from 134±3.9 mg/dL and 7.9±0.2% at baseline to 116±2.2 mg/dL and 7.4±0.2% at 12 months after starting IDeg (P<0.0001 and P≤0.001, respectively). Overall and nocturnal hypoglycemia (PG<70 mg/dL) frequencies also decreased significantly from 4.9±0.7 and 2.0±0.3 times/month to 2.4±0.3 and 0.4±0.1 times/month at 12 months after starting IDeg (P≤0.005 and P<0.0005, respectively). The daily basal insulin dose was significantly reduced from 0.48±0.04 units/kg/day at baseline to 0.38±0.03 units/kg/day at the end of the study period (P<0.0001), which corresponded to 79.2% of the baseline value. Trends were similar in patients receiving the once-daily injection and those given twice-daily injections, but basal-insulin value reductions from baseline were more marked in patients receiving twice-daily injections of basal insulin (76.0% vs. 82.6% of the baseline value). These results suggest that switching from IGlar to an appropriate dose of IDeg may effectively control hyperglycemia while reducing the frequency of hypoglycemia episodes in young Japanese people with type 1 diabetes.

Insulin resistance at diagnosis in Japanese children with type 2 diabetes mellitus.

BACKGROUND: Insulin resistance at diagnosis was investigated in Japanese children with type 2 diabetes mellitus (T2DM). METHODS: A total of 160 children with T2DM were divided into groups on the basis of percent overweight at time of diagnosis: group A (n = 28), <20%; group B (n = 55), 20-39%; group C (n = 37), 40-59%; group D (n = 40), ≥ 60%. Indicators of insulin resistance at diagnosis were compared among the four patient groups, and also between the children with T2DM and the 201 age-matched normal Japanese children. RESULTS: There were no significant differences in plasma glucose (PG) levels among the four patient groups. The mean concentration of fasting plasma immunoreactive insulin (IRI) was significantly higher in group D than in groups A and B (39.2 µU/mL vs 16.2 µU/mL and 24.1 µU/mL, P < 0.05, respectively). The mean homeostasis model assessment (HOMA-R) was significantly higher in group D than in all the other three groups (17.6 vs 7.8, 10.8 and 12.7, P < 0.05, respectively). The indicators HOMA-R and fasting IRI were significantly higher in each diabetes group, even in non-obese group A, than in normal children (P < 0.01, respectively). CONCLUSIONS: Japanese children with T2DM had insulin resistance at diagnosis regardless of percent overweight, and the degree of insulin resistance gradually increased with rise in percent overweight.

Frequent scanning using flash glucose monitoring contributes to better glycemic control in children and adolescents with type 1 diabetes.

AIMS/INTRODUCTION: We examined the impact of scanning frequency with flash glucose monitoring on glycemic control in children and adolescents with type 1 diabetes. MATERIALS AND METHODS: The study included 85 patients, aged 14.0 ± 0.5 years, with type 1 diabetes. The median time in the target glucose range (TIR) and glycosylated hemoglobin (HbA1c) values were 50.0 ± 1.4% and 7.5 ± 0.1%, respectively. RESULTS: The median scanning frequency using flash glucose monitoring was 12.0 ± 0.4 times/day. Scanning frequency showed a significant positive correlation with TIR and an inverse correlation with HbA1c. Scanning frequency was identified to be the determinant of TIR and HbA1c by using multivariate analysis. The participants whose scanning frequency was <12 times/day were categorized as the low-frequency group (n = 40), and those who carried out the scanning >12 times/day were categorized as the high-frequency group (n = 45). Patients in the high-frequency group were more likely to be treated with insulin pumps compared with those in the low-frequency group; however, this difference was not significant (21.3 vs 5.3%, P = 0.073). The high-frequency group showed significantly greater TIR than the low-frequency group (57 ± 1.6 vs 42 ± 1.7%, P = 0.002). Furthermore, the high-frequency group showed significantly lower HbA1c levels than the low-frequency group (6.8 ± 0.1 vs 8.0 ± 0.1%, P < 0.001). CONCLUSIONS: These findings showed that patients with a higher scanning frequency had better glycemic control, with greater TIRs and lower HbA1c levels, compared with those with a lower scanning frequency. Scanning frequency of >12 times/day might contribute to better glycemic outcomes in real-world practice in children with type 1 diabetes.

Comparison of the clinical effects of intermittently scanned and real-time continuous glucose monitoring in children and adolescents with type 1 diabetes: A retrospective cohort study.

AIMS/INTRODUCTION: The aim of the study was to compare two continuous glucose monitoring (CGM) systems, intermittently scanned CGM (isCGM) and real-time CGM (rtCGM), to determine which system achieved better glycemic control in pediatric patients. MATERIALS AND METHODS: We carried out a retrospective cohort study of children and adolescents with type 1 diabetes, and compared the time in range (70-180 mg/dL), time below range (<70 mg/dL) and time above range (>180 mg/dL), and estimated glycated hemoglobin levels between patients on isCGM and rtCGM. RESULTS: Of the 112 participants, 76 (67.9%) used isCGM and 36 (32.1%) used rtCGM for glycemic management. Patients on rtCGM had significantly greater time in range (57.7 ± 12.3% vs 52.3 ± 12.3%, P = 0.0368), and had significantly lower time below range (4.3 ± 2.7% vs 10.2% ± 5.4%, P < 0.001) than those on isCGM, but there was no significant difference in the time above range (37.4 ± 12.9% vs 38.0% ± 12.5%, P = 0.881) or the glycosylated hemoglobin A1c levels (7.4 ± 0.9% vs 7.5 ± 0.8%, P = 0.734) between the two groups. CONCLUSIONS: Pediatric patients with type 1 diabetes on rtCGM also showed more beneficial effects for increase of time in range, with a notable reduction of time below range compared with those on isCGM. Real-time CGM might provide better glycemic control than isCGM in children with type 1 diabetes.

Case of type 2 diabetes possibly caused by excessive accumulation of visceral fat in a child born small-for-gestational age.

We encountered a 12-year-old boy with type 2 diabetes who was born small-for-gestational age. We described his clinical characteristics and a possible etiological factor for development of hyperglycemia. He developed well with sufficient nutrition and progressed to being overweight at 6 years-of-age as a result of a high-calorie, high-protein intake diet. He showed a diabetic pattern with a normal insulin response on an oral glucose tolerance test carried out with the urine glucose screening program at schools. He showed a large total fat area of 239.4 cm2 ; in particular, his visceral fat area was 103.0 cm2 with a high ratio of visceral fat area to subcutaneous fat area (0.76). The present case might show that insulin resistance, possibly as a result of accumulation of a great amount of visceral fat, might be attributed to the pathogenesis of type 2 diabetes in children born small-for-gestational age.

Juvenile case with the coexistence of maturity-onset diabetes of the young 1 and later-onset latent autoimmune diabetes in youth.

We present the case of a 12-year-old Japanese girl, who was positive for markers of both maturity-onset diabetes of the young and latent autoimmune diabetes in youth. She was initially diagnosed with maturity-onset diabetes of the young 1 based on the molecular analysis, and she later developed an autoimmune response, leading to ß-cell-associated antibody-positive diabetes. She was treated with incretin-associated drugs and maintained adequate glycemic control. Pathophysiologically, there was an overlap between the two different types of diabetes, because the hyperglycemia and ß-cell stress seen in non-autoimmune diabetes can cause ß-cell autoimmunity over time.

Significance of "Time below Range" as a Glycemic Marker Derived from Continuous Glucose Monitoring in Japanese Children and Adolescents with Type 1 Diabetes.

INTRODUCTION: We evaluated the frequencies of various glycemic markers derived from continuous glucose monitoring in Japanese children and adolescents with type 1 diabetes and assessed the significance of hypoglycemia duration. METHODS: We enrolled 85 children and adolescents (36 boys and 49 girls) with type 1 diabetes who used FreeStyle® Libre in the present study. Frequencies of blood glucose levels as time within target range (TIR; 70-180 mg/dL), time below target range (TBR; <70 mg/dL), time below extreme hypoglycemia range (TBER; <54 mg/dL), and time above range (TAR; >180 mg/dL) were assessed during a 3-month study period. Furthermore, we evaluated the intraday frequencies of TBR and TBER. RESULTS: The mean frequencies of TIR, TBR, and TAR were 52.7 ± 11.3%, 10.8 ± 5.4%, and 36.5 ± 10.8%, respectively, whereas the mean frequency of TBER was 1.1 ± 0.9% (0-3.0%); there was no clinical episode of severe hypoglycemia. The mean frequency of TBR was significantly greater in 0-6 h (16.9 ± 5.2%) than in 6-12 h (7.8 ± 2.9%) and 18-24 h (6.8 ± 4.8%; p < 0.01) time zones, respectively. DISCUSSION/CONCLUSION: We found similar TIR and comparatively higher TBR frequencies, particularly during sleep, than those that were previously reported. Possible reasons for the higher frequency of TBR include differences in the quality of insulin treatment and diabetes care between the present study and the European studies. The utilization of advanced technologies, such as a predictive low-glucose suspend-function pump or closed-loop therapy, can reduce the frequency of TBR, with a consequent increase in TIR frequency and comprehensive improvement in glycemic control.

Zinc deficiency in Japanese children with idiopathic short stature.

Background and methods We investigated the frequency of zinc deficiency in Japanese children with idiopathic short stature, and evaluated whether serum zinc levels correlated with background factors, including age and standard deviation scores (SDSs) for height and serum insulin-like growth factor (IGF)-1 levels. The study subjects consisted of 89 Japanese children. Results The mean serum zinc level was 79 ± 12 (49-108) µg/dL. Of all the children, 48.3% had a low zinc level, in the 60-80 µg/dL range, and 6.7% had zinc deficiency with a zinc level below 60 µg/dL. The majority with a low zinc level and zinc deficiency were asymptomatic other than for short stature. We found no significant correlations of serum zinc with age, or the SDSs for height and serum IGF-1 levels, in either the entire subject population or those with a zinc level below 80 µg/dL. Conclusions We found a low zinc level to be common in Japanese children with idiopathic short stature, whereas actual zinc deficiency was rare. However, other as yet unknown mechanisms not associated with the growth hormone (GH)-IGF-1 axis could be involved in growth retardation in idiopathic short stature.

Different Risk for Hypertension, Diabetes, Dyslipidemia, and Hyperuricemia According to Level of Body Mass Index in Japanese and American Subjects.

Obesity is a risk factor for hypertension, diabetes mellitus (DM), dyslipidemia, and hyperuricemia. Here, we evaluated whether the same body mass index (BMI) for the U.S. population conferred similar metabolic risk in Japan. This was a cross-sectional analysis involving 90,047 Japanese adults (18⁻85 years) from St. Luke's International Hospital, Tokyo, Japan and 14,734 adults from National Health and Nutrition Examination Survey (NHANES) collected in the U.S. We compared the prevalence of hypertension, DM, dyslipidemia, and hyperuricemia according to BMI in Japan and the U.S. The prevalence of hypertension, DM, and dyslipidemia were significantly higher in the U.S. than Japan, whereas the prevalence of hyperuricemia did not differ between countries. Higher BMI was an independent risk factor for hypertension, DM, dyslipidemia, and hyperuricemia both in Japan and in the U.S. after adjusting for age, sex, smoking and drinking habits, chronic kidney disease, and other cardiovascular risk factors. The BMI cut-off above which the prevalence of these cardio-metabolic risk factors increased was significantly higher in the U.S. than in Japan (27 vs. 23 kg/m² for hypertension, 29 vs. 23 kg/m² for DM, 26 vs. 22 kg/m² for dyslipidemia, and 27 vs. 23 kg/m² for hyperuricemia). Higher BMI is associated with an increased prevalence of hypertension, DM, dyslipidemia, and hyperuricemia both in Japan and U.S. The BMI cut-off above which the prevalence of cardio-metabolic risk factors increases is significantly lower in Japan than the U.S., suggesting that the same definition of overweight/obesity may not be similarly applicable in both countries.

"Metabolically Healthy" Obesity and Hyperuricemia Increase Risk for Hypertension and Diabetes: 5-year Japanese Cohort Study.

OBJECTIVE: Whether obesity without metabolic syndrome (i.e., "metabolically healthy" obesity) confers similar or less metabolic risk remains controversial. METHODS: A retrospective 5-year cohort study of 9,721 Japanese subjects (48.5 ± 10.5 years, 4,160 men) was conducted in 2004 and reevaluated 5 years later. Subjects were excluded if they were hypertensive or diabetic or were receiving medications for dyslipidemia and/or gout or hyperuricemia in 2004. Study subjects were categorized according to baseline BMI ≥ 25 kg/m2 (overweight/obesity) and < 25 kg/m2 (lean/normal weight) and also whether they had metabolic syndrome. The cumulative incidence of hypertension and diabetes over 5 years between groups was assessed. A second analysis evaluated whether baseline hyperuricemia provided additional risk. RESULTS: Subjects with overweight/obesity but without metabolic syndrome carried increased cumulative incidence of hypertension (14.6% vs. 7.2%, P < 0.001) and diabetes (2.6% vs. 1.1%, P = 0.004) over 5 years compared to lean/normal subjects without metabolic syndrome. Overweight/obesity conferred an increased risk for diabetes even in individuals with normal fasting blood glucose. Hyperuricemia became an independent risk factor for developing hypertension over 5 years in lean/normal subjects without metabolic syndrome. A 1 mg/dL increase in serum uric acid carried increased risk for hypertension (19%) and diabetes (27%). CONCLUSIONS: Metabolically healthy obesity and hyperuricemia confer increased risk for hypertension and diabetes.

Efficacy and safety of switching to insulin glulisine from other rapid-acting insulin analogs in children with type 1 diabetes.

We investigated the efficacy and safety of switching to insulin glulisine (GLU) from other rapid-acting insulin analogs (Ra) in children with type 1 diabetes treated with multiple daily injections of insulin or continuous subcutaneous insulin infusion. A total of 26 children with type 1 diabetes were included. Ra in all of these patients was changed to GLU, and they were observed for a 6-month period after having previously finished treatment with other Ra. The mean glycated hemoglobin value decreased from 7.6 ± 1.0 to 7.4 ± 0.9% (P = 0.0034), and mean plasma glucose values after breakfast and supper also improved from 183 ± 50 to 153 ± 32 mg/dL (P = 0.0035), and from 203 ± 29 to 164 ± 23 mg/dL (P < 0.0001), respectively. Furthermore, the mean frequency of hypoglycemia was reduced from 7 ± 6 to 4 ± 4/month (P = 0.0004), while insulin doses and obesity degree were stable with statistically non-significant differences. In conclusion, switching to GLU might be a good treatment option for improving glycemic control in children with type 1 diabetes.

Basal insulin requirement of youth with type 1 diabetes differs according to age.

We investigated the percentage of total basal insulin dose to total daily insulin dose (%TBD) among Japanese youth of different ages with type 1 diabetes. The study enrolled 69 patients with type 1 diabetes who were treated with multiple daily injections of insulin. The participants were divided into the following age groups: group A, 0 to <10 years (n = 18); group B, 10 to <20 years (n = 31) and group C, 20 to <25 years (n = 20). We found no difference in the sex ratio, body mass index, and glycated hemoglobin and 2-h postprandial C-peptide levels among the three groups. Participants assigned to group B had a significantly higher percentage of total daily insulin dose than those in group A and group C (49.7 ± 10.4% vs 38.5 ± 13.7% and 38.3 ± 8.2%, P = 0.0005). In conclusion, the basal insulin requirements of Japanese youth with type 1 diabetes might have an age effect that is associated with puberty.

Clinical characteristics of non-obese children with type 2 diabetes mellitus without involvement of ß-cell autoimmunity.

AIMS: We examined the clinical characteristics of non-obese Japanese children with type 2 diabetes mellitus (T2DM) not associated with ß-cell autoimmunity. METHODS: Of 218 children who were diagnosed as having T2DM by a school urine glucose screening program in Tokyo, 24 were identified as being non-obese and were enrolled in this study. None of the children had any evidence of ß-cell autoimmunity or genetic disorders. RESULTS: The mean ages at diagnosis and at the study were 12.5 ± 1.7 and 22.4 ± 5.7 years, respectively. Females were predominant (M/F ratio: 4/20). Family history of T2DM, mostly of the non-obese type, was present in 62.5% of the cases. In regard to the birth weight, 20.8% had a history of low birth weight, and 8.3% were large for gestational age. The mean fasting insulin level, HOMA-R, HOMA-ß, and an insulinogenic index on the OGTT at the time of diagnosis were 11.8 ± 7.8 µU/ml, 5.4 ± 3.8, 96.1 ± 55.0 and 0.16 ± 0.14, respectively. Most patients were treated by either oral hypoglycemic drug (45.8%) or insulin (50.0%) therapy at the study, with the mean interval to the start of pharmacological treatment of 3.1 ± 2.3 years. CONCLUSIONS: Non-obese children with T2DM seemed to show lower insulin secretory capacities with mild, but evident, insulin resistance even from the time of diagnosis, and also earlier requirement of pharmacological therapies during the clinical course. Some genetic factors not associated with autoimmunity may play a role in the etiology of T2DM in non-obese children.