Autoimmune diabetes is a heterogeneous disease which can arise at any age. Subjects with adult-onset autoimmune diabetes who do not necessitate insulin-therapy for at least 6 months after diagnosis are demarcated as having latent autoimmune diabetes in adults (LADA). This condition is more heterogeneous than young-onset autoimmune diabetes and shares clinical and metabolic characteristics with both type 2 and type 1 diabetes. Patients with LADA are considered by having highly variable β-cell destruction, different degrees of insulin resistance and heterogeneous titre and pattern of islet autoantibody, suggesting different pathophysiological pathways partially explaining the heterogeneous phenotypes of LADA. To date the heterogeneity of LADA does not allow to establish a priori treatment algorithm and no specific guidelines for LADA therapy are available. These subjects are mostly treated as affected by type 2 diabetes, a factor that might lead to the progression to insulin-dependency quickly. A personalised medicine approach is necessary to attain optimal metabolic control and preserve β-cell function to decrease the risk of long-term diabetes complications. Recent data concerning the use of oral antidiabetic agents as dipeptidyl peptidase 4 inhibitors and glucagon-like peptide 1 receptor agonists indicate up-and-coming results in term of protect C-peptide levels and improving glycaemic control. This review summarises current knowledge on LADA, emphasising controversies regarding its pathophysiology and clinical features. Moreover, we discuss data available about novel therapeutic approaches that can be considered for prevention of β-cell loss in LADA.
Adult* ; Autoantibodies ; C-Peptide ; Diabetes Complications ; Diabetes Mellitus, Type 1* ; Diabetes Mellitus, Type 2 ; Diagnosis ; Dipeptidyl-Peptidase IV Inhibitors ; Glucagon-Like Peptide 1 ; Humans ; Hypoglycemic Agents ; Insulin ; Insulin Resistance ; Islets of Langerhans ; Phenotype ; Population Characteristics

Dietary fiber improves hyperglycemia in patients with type 2 diabetes through its physicochemical properties and possible modulation of gut hormone secretion, such as glucagon-like peptide 1 (GLP-1). We assessed the effect of dietary fiber-enriched cereal flakes (DC) on postprandial hyperglycemia and gut hormone secretion in patients with type 2 diabetes. Thirteen participants ate isocaloric meals based on either DC or conventional cereal flakes (CC) in a crossover design. DC or CC was provided for dinner, night snack on day 1 and breakfast on day 2, followed by a high-fat lunch. On day 2, the levels of plasma glucose, GLP-1, glucose-dependent insulinotropic polypeptide (GIP), and insulin were measured. Compared to CC, DC intake exhibited a lower post-breakfast 2-hours glucose level (198.5±12.8 vs. 245.9±15.2 mg/dL, P<0.05) and a lower incremental peak of glucose from baseline (101.8±9.1 vs. 140.3±14.3 mg/dL, P<0.001). The incremental area under the curve (iAUC) of glucose after breakfast was lower with DC than with CC (P<0.001). However, there were no differences in the plasma insulin, glucagon, GLP-1, and GIP levels. In conclusion, acute administration of DC attenuates postprandial hyperglycemia without any significant change in the representative glucose-regulating hormones in patients with type 2 diabetes (ClinicalTrials.gov. NCT 01997281).
Adult ; Aged ; Area Under Curve ; Blood Glucose/*analysis ; Cross-Over Studies ; Diabetes Mellitus, Type 2/complications/diagnosis/*diet therapy ; Dietary Fiber/*therapeutic use ; Female ; Gastric Inhibitory Polypeptide/blood ; Glucagon/blood ; Glucagon-Like Peptide 1/*blood ; Hemoglobin A, Glycosylated/analysis ; Humans ; Hyperglycemia/complications/diagnosis ; Insulin/blood ; Intestines/metabolism ; Male ; Middle Aged ; ROC Curve

Glycogenic hepatopathy (GH) is an uncommon cause of serum transaminase elevation in type I diabetes mellitus (DM). The clinical signs and symptoms of GH are nonspecific, and include abdominal discomfort, mild hepatomegaly, and transaminase elevation. In this report we describe three cases of patients presenting serum transaminase elevation and hepatomegaly with a history of poorly controlled type I DM. All of the cases showed sudden elevation of transaminase to more than 30 times the upper normal range (like in acute hepatitis) followed by sustained fluctuation (like in relapsing hepatitis). However, the patients did not show any symptom or sign of acute hepatitis. We therefore performed a liver biopsy to confirm the cause of liver enzyme elevation, which revealed GH. Clinicians should be aware of GH so as to prevent diagnostic delay and misdiagnosis, and have sufficient insight into GH; this will be aided by the present report of three cases along with a literature review.
Acute Disease ; Adult ; Alanine Transaminase/blood ; Aspartate Aminotransferases/blood ; Delayed Diagnosis ; Diabetes Mellitus, Type 1/complications/*pathology ; Diagnostic Errors ; Female ; Glycogen Storage Disease/complications/*diagnosis/ultrasonography ; Hepatitis/diagnosis ; Hepatomegaly/complications/*diagnosis/ultrasonography ; Humans ; Liver/pathology ; Recurrence ; Young Adult

A 21-year-old man with diabetic ketoacidosis (DKA) displayed short and clubbed fingers and marked eyebrow, which are typical of Hajdu-Cheney Syndrome (HCS). Laboratory findings confirmed type 1 diabetes mellitus (DM). After conservative care with hydration and insulin supply, metabolic impairment was improved. Examinations of bone and metabolism revealed osteoporosis and craniofacial abnormalities. The mutation (c.6443T>G) of the NOTCH2 gene was found. The patient was diagnosed with HCS and DM. There may be a relationship between HCS and DM, with development of pancreatic symptoms related to the NOTCH2 gene mutation.
Adult ; Bone Density ; Craniofacial Abnormalities/complications/radiography ; Diabetes Mellitus, Type 1/*complications/diagnosis ; Diabetic Ketoacidosis/complications/genetics ; Glycosuria ; Hajdu-Cheney Syndrome/*complications/diagnosis/radiography ; Humans ; Ketone Bodies/urine ; Male ; Mutation ; Osteoporosis/complications/radiography ; Receptor, Notch2/*genetics ; Young Adult

Diabetes Mellitus, Type 1 ; diagnosis ; etiology ; Humans ; Klinefelter Syndrome ; complications ; diagnosis ; Male

This study was done to characterize the natural course of C-peptide levels in patients with type 1 diabetes and identify distinguishing characters among patients with lower rates of C-peptide decline. A sample of 95 children with type 1 diabetes was analyzed to retrospectively track serum levels of C-peptide, HbA1c, weight, BMI, and diabetic complications for the 15 yr after diagnosis. The clinical characteristics were compared between the patients with low and high C-peptide levels, respectively. The average C-peptide level among all patients was significantly reduced five years after diagnosis (P < 0.001). The incidence of diabetic ketoacidosis was significantly lower among the patients with high levels of C-peptide (P = 0.038). The body weight and BMI standard deviation scores (SDS) 15 yr after diagnosis were significantly higher among the patients with low C-peptide levels (weight SDS, P = 0.012; BMI SDS, P = 0.044). In conclusion, C-peptide level was significantly decreased after 5 yr from diagnosis. Type 1 diabetes patients whose beta-cell functions were preserved might have low incidence of diabetic ketoacidosis. The declines of C-peptide level after diagnosis in type 1 diabetes may be associated with changes of body weight and BMI.
Adolescent ; Body Mass Index ; Body Weight ; C-Peptide/*blood ; Child ; Child, Preschool ; Diabetes Complications ; Diabetes Mellitus, Type 1/blood/*diagnosis ; Diabetic Ketoacidosis/epidemiology ; Diabetic Retinopathy/epidemiology ; Female ; Follow-Up Studies ; Hemoglobin A, Glycosylated/analysis ; Humans ; Incidence ; Infant ; Male ; Peripheral Nervous System Diseases/epidemiology ; Retrospective Studies

Klinefelter’s syndrome (KS) is the most common sex chromosome disease in men. Classical features of the syndrome include a eunuchoidal body habitus, small testes and hypergonadotrophic hypogonadism. There has been an increased risk of diabetes mellitus and autoimmune disease for KS patients. This paper reports a case of KS in association with type 1 diabetes mellitus. The patient was a 21-year-old man, who has been confirmed by absolute insulin deficiency and positive IA-2 autoantibody. The hyperinsulinemic euglycemic clamp test indicated his insulin sensitivity in normal range, and his blood glucose was controlled well by the insulin therapy.
Adult ; Diabetes Mellitus, Type 1 ; diagnosis ; etiology ; Humans ; Klinefelter Syndrome ; complications ; diagnosis ; Male ; Young Adult

OBJECTIVETo review the incident status of childhood type 1 diabetes mellitus hospitalized in the Children's Hospital of Zhejiang University School of Medicine from 1999 to 2009 and to explore the clinical value of IL-10 in diabetic ketoacidosis.

METHODSThe clinical data of 263 children with type 1 diabetes mellitus hospitalized in the Children's Hospital of Zhejiang University School of Medicine from January 1999 to February 2009 were retrospectively reviewed. Serum lipid levels were measured in 48 children with type 1 diabetes mellitus and in 24 healthy children. The diabetic children were classified into two subgroups, with or without ketoacidosis. Serum lipid and cytokines levels were compared.

RESULTSChildhood type 1 diabetes mellitus was common in females (56.3%). The peak incident age of the disease was between 6 and 11.9 years. Diabetic ketoacidosis was as the presenting symptom for the first visit in 86 cases (32.7%). The levels of serum lipid, blood glucose and HbA1c in diabetic children with ketoacidosis were significantly higher than those without ketoacidosis (P<0.05). Logistic analysis demonstrated that the increased levels of blood glucose, serum lipid and HbA1c were risk factors for diabetic ketoacidosis. The level of serum IL-10 in diabetic children with ketoacidosis was significantly higher than that in patients without ketoacidosis (P<0.01), while there were no differences in serum levels IL-2, IL4, IL-6, TNF-α and IFN-γ between them. Serum levels IL-2, IL-4, IL-6, IL-10, TNF-α and IFN-γ in diabetic children were significantly higher than those in healthy children (P<0.01).

CONCLUSIONSKetoacidosis is a common acute complication of type 1 diabetes mellitus. The disorders of glucose and lipid metabolism are the risk factors for ketoacidosis in diabetic children. IL-10 may be a sensitive index of diabetic ketoacidosis in children with type 1 diabetes mellitus.

Adolescent ; Child ; Child, Preschool ; Diabetes Mellitus, Type 1 ; blood ; complications ; Diabetic Ketoacidosis ; blood ; diagnosis ; Female ; Humans ; Infant ; Interleukin-10 ; blood ; physiology ; Logistic Models ; Male ; Retrospective Studies

INTRODUCTIONThis study aims to evaluate the results of foot screening performed in a study population of 2137 diabetics (3926 feet) screened from 2006 to 2008 by the National University Hospital (NUH) multi-disciplinary team for diabetic foot problems.

MATERIALS AND METHODSA standardised protocol was designed. Foot screening consisted of detailed history taking and clinical examination including assessment for sensory neuropathy by Semmes Weinstein monofilament (SWMF) and neurothesiometer and assessment of vasculopathy by ankle-brachial index (ABI) and total body irradiation (TBI). The foot screening was performed by a trained staff nurse. All patients were classified according to King's College Classification.

RESULTSMajority of the patients were in the fifth (27.9%) and sixth (30.0%) decades of life. Two thousand sixty-four had type II diabetes, and only 73 had type I diabetes. Neuropathy was found in 1307 (33.3%) feet based on 5.07 SWMF. Vasculopathy was recorded in 510 (13.0%) and 546 (13.9%) feet based on ABI <0.8 and TBI <0.7. According to King's Classification, 1069 (50.0%) were Stage 1: Normal and 615 (28.8%) were Stage 2: At-Risk.

CONCLUSIONFoot screening should be performed as early as possible to detect "At-Risk" feet and prevent the development of diabetic foot complications, thereby further reducing the risk of major amputations.

Adolescent ; Adult ; Aged ; Child ; Comorbidity ; Diabetes Mellitus, Type 1 ; complications ; epidemiology ; Diabetes Mellitus, Type 2 ; complications ; epidemiology ; Diabetic Foot ; classification ; diagnosis ; Female ; Humans ; Male ; Mass Screening ; methods ; Middle Aged ; Prospective Studies ; Referral and Consultation ; Young Adult

We report a case of diabetic ketoacidosis (DKA) and hypertriglyceridemia (severely elevated to 15,240 mg/dL) complicated by acute pancreatitis, which was treated successfully with insulin therapy and conservative management. A 20-yr-old woman with a history of type 1 diabetes came to the emergency department 7 months after discontinuing insulin therapy. DKA, severe hypertriglyceridemia and acute pancreatitis were diagnosed, with DKA suspected of contributing to the development of the other conditions. In Korea, two cases of DKA-induced hypertriglyceridemia and 13 cases of hypertriglyceridemia-induced acute pancreatitis have been previously reported separately.
Acute Disease ; Diabetes Mellitus, Type 1/complications/diagnosis/therapy ; Diabetic Ketoacidosis/complications/*diagnosis/therapy ; Female ; Humans ; Hypertriglyceridemia/complications/*diagnosis/therapy ; Insulin/therapeutic use ; Pancreatitis/complications/*diagnosis ; Tomography, X-Ray Computed ; Young Adult