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PubMed1990

Scope and heterogeneous nature of MODY.

This review summarizes aspects of the phenotypic expression, natural history, recognition, pathogenesis, and heterogeneous nature of maturity-onset diabetes of the young (MODY), which is inherited in an autosomal-dominant pattern. There are differences in metabolic, hormonal, and vascular abnormalities in different ethnic groups and even among White pedigrees. In MODY patients with low insulin responses, there are delayed and decreased insulin and C-peptide secretory responses to glucose from childhood or adolescence even before glucose intolerance appears, which may represent the basic genetic defect. When followed for decades, nondiabetic siblings have normal insulin responses. The fasting hyperglycemia of some MODY patients has been treated successfully with sulfonylureas for up to 30 yr. In a few patients, after years or decades of diabetes, the insulin and C-peptide responses to glucose are so low that they resemble those of early insulin-dependent diabetes mellitus. The progression of the insulin secretory defect over time distinguishes between these two types of diabetes. In contrast are patients from families who have very high insulin responses to glucose, despite glucose intolerance and fasting hyperglycemia similar to that seen in patients with low insulin responses. In many of these patients, there is in vivo and in vitro evidence of insulin resistance. Whatever its mechanism, the compensatory insulin responses to nutrients must be insufficient to maintain normal carbohydrate tolerance. This suggests that diabetes occurs only in those patients who have an additional islet cell defect, i.e., insufficient beta-cell reserve and secretory capacity. In a few MODY pedigrees with high insulin responses to glucose and lack of evidence of insulin resistance, a structurally abnormal mutant insulin molecule that is biologically ineffective is secreted. No associations have been found between specific HLA antigens and MODY in White, Black, and Asian pedigrees. Linkage studies of the insulin gene, insulin-receptor gene, erythrocyte/HepG2 glucose-transporter locus, and apolipoprotein B locus have shown no association with MODY. Vascular disease may be as prevalent as in conventional non-insulin-dependent diabetes mellitus. Because of autosomal-dominant transmission and penetrance at a young age, MODY is a good model for further investigations of etiologic and pathogenetic factors in non-insulin-dependent diabetes mellitus, including the use of genetic linkage strategies to identify diabetogenic genes.

Adult↗
PubMed1999

Phenotypic characteristics of early-onset autosomal-dominant type 2 diabetes unlinked to known maturity-onset diabetes of the young (MODY) genes.

OBJECTIVE: To investigate whether there are forms of early-onset autosomal-dominant type 2 diabetes that are distinct from typical maturity-onset diabetes of the young (MODY) and to characterize their phenotypic characteristics. RESEARCH DESIGN AND METHODS: The study included 220 affected subjects from 29 families in which early-onset type 2 diabetes occurred in multiple generations and was not linked to known MODY genes (MODY gene-negative families). All individuals underwent an oral glucose tolerance test and other clinical measurements aimed at investigating the underlying metabolic defect and the presence of diabetic complications. For comparison, 79 affected carriers of MODY3 (hepatocyte nuclear factor [HNF]-1 alpha) mutations were similarly examined. RESULTS: Subjects from MODY gene-negative pedigrees were diagnosed with diabetes at an older age (36 +/- 17 vs. 21 +/- 10 years, P = 0.0001) and were more frequently obese (52 vs. 18%, P = 0.0001) than MODY3 individuals. MODY gene-negative patients who were insulin treated required more exogenous insulin than did MODY3 subjects (0.7 +/- 0.4 vs. 0.45 +/- 0.2 U.kg-1.day-1, P = 0.04), despite similar C-peptide levels. Among subjects not treated with insulin, MODY gene-negative subjects had significantly higher serum insulin levels, both fasting (16.5 +/- 15 vs. 6.5 +/- 5 microU/ml, P = 0.027) and 2 h after a glucose load (53 +/- 44 vs. 11 +/- 10, P = 0.002). They also had higher serum triglycerides (P = 0.02), higher cholesterol levels (P = 0.02), more hypertension (P = 0.0001), and more nephropathy (P = 0.001). Differences persisted when families were matched for age at diagnosis. CONCLUSIONS: Our findings indicate the existence of forms of early-onset autosomal-dominant type 2 diabetes that are distinct from MODY and are frequently characterized by insulin resistance, similar to later-onset type 2 diabetes. Because of the Mendelian pattern of inheritance, the goal of identifying the genes involved in these forms of diabetes appears to be particularly feasible.

Adult↗
PubMed2004

Spectrum of HNF1A and GCK mutations in Canadian families with maturity-onset diabetes of the young (MODY).

PURPOSE: Maturity-onset diabetes of the young (MODY) is a subtype of type 2 diabetes characterized by autosomal-dominant inheritance and early onset. The pathophysiology of MODY is primarily defective insulin secretion resulting from mutations in at least 6 different genes. Most affected patients harbour mutations in either GCK (encoding glucokinase, also called MODY2) and HNF1A (encoding hepatic nuclear factor-1alpha, also called MODY3). We studied Canadian probands to determine if they had mutations in MODY2 or MODY3 genes. METHOD: We used genomic DNA sequencing of probands from 9 previously unreported Canadian MODY families. RESULTS: Five MODY probands had mutations in HNF1A, of which 4 were novel (namely IVS5-1delTAG, E275fsdelGAAG, F268S and L44fsdelC) and 4 had mutations in GCK, of which 2 were novel (E237K and L324P). These mutations expand the spectrum of MODY mutations and bring the total number of Canadian MODY families that have been molecularly defined in our laboratory to 15 (8 MODY3 and 7 MODY2). CONCLUSION: Because of the growing evidence that molecular diagnosis may affect prognosis and treatment, this information may be important in future for Canadian MODY families and their physicians.

Adolescent↗
PubMedDate not supplied

An underdiagnosed type of diabetes: the MODY syndromes. Pathophysiology, clinical presentation and renal disease progression.

Maturity onset diabetes of the young (MODY syndrome) is characterized by a non-ketotic type II diabetes mellitus (DM) that is inherited by an autosomal dominant mode and appears in young people, <25 yrs old, with a prominent family history of DM in successive generations from one side of the parents. Usually, it presents as asymptomatic mild hyperglycemia, which can be undetected for prolonged periods. Therefore, diagnosis can be made rather late in adulthood and diabetic complications could be present at diagnosis. It is estimated that it could account for 1-5% of cases in the US and other industrialized countries and can result from mutations on any of six different genes that are expressed in the beta-cells of the pancreas. These genes encode the glycolytic enzyme glucokinase (MODY 2) and the other five encode the transcription factors hepatocyte nuclear factor (HNF) 4alpha (MODY 1), HNF-1alpha (MODY 3), HNF-1beta (MODY 5), insulin promoter factor 1 (IPF-1) (MODY 4) and neurogenic differentiation factor-1 (NeuroD1) (MODY 6).

Adult↗
PubMedDate not supplied

[MODY types of diabetes mellitus].

Maturity-onset diabetes of the young (MODY) is a monogenic subtype of diabetes mellitus characterized by a young onset of type 2 diabetes, some abnormalities of the beta-cell function and an autosomal dominant inheritance with high penetrance. MODY types represent less than 5% of all cases of type 2 diabetes. Six genetic mutations have been described, one of them affecting the glucokinase gene (MODY 2) and the others various transcription factors HNF-1alpha, HNF-4alpha, HNF-1beta, IPF-1 and NeuroD (MODY 1,3,4,5,6, respectively). These different underlying gene mutations are associated with different clinical forms of the disease. Among the two most frequent forms, MODY 2 (mutation of the glucokinase gene) has a benign clinical evolution whereas MODY 3 (mutation of HNF-1alpha gene) has a much more severe evolution. The recognition of the MODY diabetes is important in clinical practice and may lead to the discovery of new more specific molecular therapeutic targets.

Age of Onset↗
PubMed1998

A nonsense mutation (R242X) in the branched-chain alpha-keto acid dehydrogenase E1alpha subunit gene (BCKDHA) as a cause of maple syrup urine disease. Mutations in brief no. 160. Online.

Mutation analysis of DNA from cultured amniocytes with absent branched-chain alpha-ketoacid dehydrogenase activity revealed a C to T transition producing a nonsense mutation (R242X) in exon 7 of the gene encoding the E1a subunit of this multienzme complex (BCKDHA). This pregnancy occured in a large consanguinous pedigree with mutiple individuals with maple syrup urine disease (MSUD). PCR amplification of the region surrounding exon 7 allowed the identification of this mutation as well as two other previously identified mutations which cause MSUD.

3-Methyl-2-Oxobutanoate Dehydrogenase (Lipoamide)↗
PubMed2005

Molecular genetics and phenotypic characteristics of MODY caused by hepatocyte nuclear factor 4alpha mutations in a large European collection.

AIMS/HYPOTHESIS: Heterozygous mutations in the gene of the transcription factor hepatocyte nuclear factor 4alpha (HNF-4alpha) are considered a rare cause of MODY with only 14 mutations reported to date. The description of the phenotype is limited to single families. We investigated the genetics and phenotype of HNF-4alpha mutations in a large European Caucasian collection. METHODS: HNF-4alpha was sequenced in 48 MODY probands, selected for a phenotype of HNF-1alpha MODY but negative for HNF-1alpha mutations. Clinical characteristics and biochemistry were compared between 54 HNF-4alpha mutation carriers and 32 familial controls from ten newly detected or previously described families. RESULTS: Mutations in HNF-4alpha were found in 14/48 (29%) probands negative for HNF-1alpha mutations. The mutations found included seven novel mutations: S34X, D206Y, E276D, L332P, I314F, L332insCTG and IVS5nt+1G>A. I314F is the first reported de novo HNF-4alpha mutation. The average age of diagnosis was 22.9 years with frequent clinical evidence of sensitivity to sulphonylureas. Beta cell function, but not insulin sensitivity, was reduced in diabetic mutation carriers compared to control subjects (homeostasis model assessment of beta cell function 29% p<0.001 vs controls). HNF-4alpha mutations were associated with lower apolipoprotein A2 (p=0.001), A1 (p=0.04) and total HDL-cholesterol (p=0.02) than in control subjects. However, in contrast to some previous reports, levels of triglycerides and apolipoprotein C3 were normal. CONCLUSIONS/INTERPRETATION: HNF-4alpha mutations are common when no HNF-1alpha mutation is found in strictly defined MODY families. The HNF-4alpha clinical phenotype and beta cell dysfunction are similar to HNF-1alpha MODY and are associated with reduced apolipoprotein A2 levels. We suggest that sequencing of HNF-4alpha should be performed in patients with clinical characteristics of HNF-1alpha MODY in whom mutations in HNF-1alpha are not found.

Adolescent↗
PubMed2001

Routine mutation screening of HNF-1alpha and GCK genes in MODY diagnosis: how effective are the techniques of DHPLC and direct sequencing used in combination?

AIMS/HYPOTHESIS: Mutations in the hepatocyte nuclear factor (HNF)-1alpha and glucokinase (GCK) genes are the major causes of monogenic forms of Type II (non-insulin-dependent) diabetes mellitus (Maturity-Onset Diabetes of the Young subtypes, MODY). We evaluated the effectiveness of fluorescent single-strand conformation polymorphism (F-SSCP), denaturing high-performance liquid chromatography (DHPLC) and sequencing based mutation detection in the molecular diagnosis of MODY. Our goal is to identify a rapid, efficient and cost effective mutation detection method for the molecular diagnosis of MODY and other human genetic disorders. METHODS: We evaluated the accuracy of DHPLC in screening for MODY 2 and 3 mutations. In addition, we compared the sensitivity, specificity, cost, handling time and analysis time of fluorescent single-strand conformation polymorphism, denaturing high-performance liquid chromatography and direct sequencing screening methods. RESULTS: Denaturing high-performance liquid chromatography is a recently developed method for mutation detection. It is cost effective, powerful and reliable and quite suitable for 22 out of the 24 fragments required for MODY 2 and 3 testing. However, exons 1 and 7 of the HNF-1alpha gene are very polymorphic and so direct sequencing is faster as well as more efficient and reliable. CONCLUSION/INTERPRETATION: Our results suggest that combining denaturing high-performance liquid chromatography and direct sequencing is a good approach for the routine detection of HNF-1alpha and GCK mutations in MODY families. Denaturing high-performance liquid chromatography appears to be a powerful tool in genetic testing and the method could be applied to the molecular diagnosis of other human genetic diseases.

Base Sequence↗
PubMed2004

First UK survey of paediatric type 2 diabetes and MODY.

AIMS: To estimate the UK prevalence of childhood type 2 diabetes and maturity onset diabetes of the young (MODY), and distinguish them from each other and from type 1 diabetes. METHODS: The British Society for Paediatric Endocrinology and Diabetes Clinical Trials/Audit Group undertook a cross-sectional questionnaire survey of all paediatric diabetes centres during 2000, collecting data on all children with non-type 1 diabetes. RESULTS: Of 112 children reported to the survey, 25 had type 2 diabetes and 20 had MODY. In contrast to type 1, type 2 patients presented later (12.8 v 9.3 years), were usually female, overweight, or obese (92% v 28%), and a greater proportion were of ethnic minority origin (56% v 22%). In contrast to type 2, MODY patients were younger (10.8 years), less likely to be overweight or obese (50% v 92%), and none were from ethnic minority groups. The crude minimum UK prevalence of type 2 diabetes under 16 years is 0.21/100 000, and of MODY is 0.17/100 000. South Asian children have a relative risk of type 2 diabetes of 13.7 compared to white UK children. CONCLUSIONS: UK children still have a low prevalence of type 2 diabetes. Children from ethnic minorities are at significantly higher risk, but in white UK children with non-type 1 diabetes a diagnosis of MODY is as likely as type 2 diabetes. Childhood type 2 diabetes is characterised by insulin resistance, and is distinct from both type 1 and MODY.

Adolescent↗
PubMedDate not supplied

[Mature onset diabetes of the young (MODY)].

Maturity-onset diabetes of the young (MODY) is a rare form of juvenile diabetes mellitus, defined by early onset, absence of ketosis, non-insulin-dependent diabetes and autosomal dominant inheritance. Advances in molecular genetic analysis have identified mutations accounting for different MODY subtypes, all of them associated with defects of insulin secretion. We present a case of a nine year-old boy, admitted to our outpatient clinic because of mild and intermittent osmotic symptoms (polyuria, polyphagia and polydipsia) and persistently high values of fasting blood glucose in the last year. He had a family history of diabetes in three consecutive generations compatible with autossomal dominant inheritance. His height was 138.5 cm (90th centile) and his weight was 33.5 Kg (90th centile). General examination was unremarkable, in a prepubertal boy. A standard oral glucose tolerance test was performed. The fasting blood glucose was 118 mg/dl with a two hour value of 160 mg/dl. ICA, IAA and GAD autoantibodies were undetectable. He started on diet therapy, keeping his fasting blood glucose measurements on the upper limits of normal and HbA1c in the normal range. He was diagnosed as having MODY 2 on a clinical basis, as it is not possible to perform molecular analysis of this pathology in Portugal. As MODY is recently thought to account for 2-5% of all cases of type 2 Diabetes Mellitus it is important to consider it as a possible diagnosis in children who present with incidental hyperglycaemia. Molecular genetic testing is very important as it enables us to make a firm diagnosis of MODY, to define a follow up plan and to reassure patients families, once the prognosis is significantly different among the different sub-types of MODY. We emphathize the need of creating national and international reference centres where such testing can be done.

Blood Glucose↗
PubMed1992

Linkage analysis of maturity-onset diabetes of the young (MODY): genetic heterogeneity and nonpenetrance.

We have analyzed the inheritance of maturity-onset diabetes of the young (MODY) on chromosome 20 in a large multigeneration family, the R.-W. family, and in two other MODY families. Of the four branches of the R.-W. pedigree which have been studied, two have documented early onset of non-insulin-dependent diabetes mellitus (NIDDM), while there is no evidence of early onset in the other two branches. The early-onset branches have apparently inherited the same D20S16 allele from the affected parent, while another D20S16 allele was inherited in the two branches without evidence of early onset. A test for homogeneity, the M-test, using the results of two-point linkage analysis with D20S16 indicates heterogeneity between early- and late-onset branches of the R.-W. family (P less than or equal to .014). In addition, analysis strongly suggests that MODY as expressed in the EDI and WIS families is unlinked to loci on chromosome 20 (P less than or equal to .018-.004). Comparable results are seen when the data are analyzed by the HOMOG program. Three polymorphic loci-D20S16, D20S17, and ADA--show no recombination with the MODY locus when two-point linkage analysis is used in the early-onset branches of the family. The multipoint lod score in the early-onset branches of the R.-W. family is 10.16, with the most likely location being between D20S4 and D20S17. Multipoint linkage analysis using the CHROMPICS option of the program CRI-MAP has been used to follow inheritance of the MODY disease locus. This analysis has identified two cases of possible nonpenetrance in the early-onset branches of the family (odds of at least 156:1), as determined by the appearance of apparent isolated double crossovers at the MODY locus in these unaffected individuals.

Adolescent↗
PubMed2002

GCK and HNF1A mutations in Canadian families with maturity onset diabetes of the young (MODY).

Maturity onset diabetes of the young (MODY) is a genetically heterogeneous form of type 2 diabetes that is characterized by autosomal dominant inheritance, onset in early adulthood and a primary defect in insulin secretion. Mutations in at least six genes have been shown to underlie MODY, including mutations in GCK (encoding glucokinase, also called MODY2) and mutations in HNF1A (encoding hepatocyte nuclear factor-1alpha, also called MODY3). We sequenced genomic DNA from probands of seven Canadian MODY families. In four probands, we detected four novel GCK mutations, namely IVS2-7G>A, G72R, T206R and S263P. In three other probands, we detected three HNF1A mutations, of which two were novel, namely 1051delCA and Q250X, and one had been previously reported, namely R131Q. The novel mutations expand the spectrum of MODY mutations. In addition, knowledge of the specific defect can be used to pre-symptomatically identify family members at risk for developing MODY.

Adolescent↗
PubMed2000

No diabetes-associated mutations in the coding region of the hepatocyte nuclear factor-4gamma gene (HNF4G) in Japanese patients with MODY.

AIMS/HYPOTHESIS: Mutations in the transcription factor hepatocyte nuclear factor (HNF)-4alpha are the cause of one form of maturity-onset diabetes of the young, MODY1. The HNF-4gamma is structurally related to HNF-4alpha and is expressed together with HNF-4alpha in pancreatic islets. We therefore tested the hypothesis that genetic variation in the HNF-4gamma gene (HNF4G) is associated with MODY in Japanese subjects. METHODS: We screened the protein coding region of HNF4G (exons 3-11) for mutations in 57 unrelated Japanese subjects with MODY by amplifying each exon and adjacent intron region using the polymerase chain reaction (PCR) and specific primers and then directly sequencing the PCR products. The frequency of each variant was compared between patients with MODY and a group of non-diabetic subjects. RESULTS: We found ten sequence variants, two of these were located in exons: exon 6, a silent substitution in codon 144, c.432A/G and exon 7, a G-to-A substitution in codon 190 (c.570G/A) resulting in a conservative Met-to-Ile substitution (M/I190) in the putative ligand-binding region of HNF-4gamma protein. The remaining eight variants were located in introns. There was no significant difference in the frequency of these polymorphisms between subjects with MODY and non-diabetic control subjects. CONCLUSION/INTERPRETATION: Genetic variation in the coding region of HNF4G is unlikely to be a major cause of MODY in Japanese people.

Amino Acid Sequence↗
PubMed2000

Molecular and biochemical analysis of the MODY syndromes.

Maturity onset diabetes of the young (MODY) is characterized by youth-onset diabetes that is inherited in an autosomal dominant (monogenic) pattern. Classic MODY accounts for less than 5% of cases of childhood diabetes in Caucasians, presents prior to age 25 years, is nonketotic, and may not require insulin treatment. A variant form of MODY that lacks a clearly defined genetic basis occurs in African Americans [atypical diabetes mellitus (ADM)] clinically presents more acutely and is initially insulin requiring. To date, five molecular causes of classic MODY have been identified: hepatocyte nuclear factor-4 alpha (HNF-4 alpha; MODY1), glucokinase (MODY2), hepatocyte nuclear factor-1 alpha (HNF-1 alpha; MODY3), insulin promoter factor-1 (IPF-1, MODY4), and hepatocyte nuclear factor-1 beta (HNF-1 beta; MODY5). MODY is studied as a model of beta cell hypofunction and modest insulinopenia. Clinical recognition of ADM is important for patient management to avoid confusion with type 1 diabetes mellitus.

Journal Article↗
PubMed1988

Pregnancy outcome in maturity onset diabetes at young age (MODY).

Diabetes mellitus is not a single disease, but rather a syndrome comprised of a variety of diseases characterized by hyperglycaemia. Indeed it has a heterogeneous nature. Maturity Onset Diabetes of the Young or MODY is an unusual, mild type of hyperglycaemia, which develops in young women, (below the age of 25), who do not require insulin. This study describes 10 pregnancies in MODY women, who are compared to a group of patients with insulin-dependent diabetes mellitus (IDDM), a group with gestational diabetes, and a control group of normal, healthy pregnant women. Our group of pregnant MODY patients proved to have an intermediate form of diabetes, more severe than gestational diabetes and yet not as severe as insulin-dependent diabetes mellitus. Mean duration of diabetes was shorter and mean daily insulin requirement (during pregnancy) was lower among MODY patients in comparison to IDDM gestants. Moreover the frequency of maternal complications and Caesarean deliveries in MODY patients were lower than in the IDDM group, but higher when compared to the gestational diabetes group.

Adolescent↗
PubMed2002

Maturity-onset diabetes of the young (MODY): genetic and clinical characteristics.

Maturity-onset diabetes of the young (MODY) is a genetically and clinically heterogeneous subtype of familial diabetes mellitus characterized by early onset, autosomal dominant inheritance and primary defects of insulin secretion. Mutations in six genes cause most of the MODY cases. These genes encode the enzyme glucokinase and the transcription factors hepatocyte nuclear factor 4alpha, hepatocyte nuclear factor 1alpha, insulin promoter factor-1, hepatocyte nuclear factor 1beta and neuroD1. Additional MODY genes remain to be identified. The study of families with MODY has shown that the different MODY subtypes present different metabolic and clinical profiles.

Age of Onset↗
PubMed2002

Nine novel mutations in maturity-onset diabetes of the young (MODY) candidate genes in 22 Spanish families.

The aims of this study were to estimate the prevalence of major maturity-onset diabetes of the young (MODY) subtypes in Spanish MODY families and to analyze genotype-phenotype correlations. Twenty-two unrelated pediatric MODY patients and 97 relatives were screened for mutations in the coding region of the glucokinase (GCK), hepatic nuclear factor- HNF-1alpha and HNF4alpha genes using PCR-single strand conformation polymorphism and/or direct sequencing. In families carrying GCK mutations, the influence of genetic defects on fetal growth was investigated by comparing the birth weights of 32 offspring discordant for the mutations. Mutations in MODY genes were identified in 64% of the families. GCK/MODY2 mutations were the most frequently found, in 41%: seven novel (R369P, S411F, M298K, C252Y, Y108C, A188E, and S383L) and 2 already described mutations. Four pedigrees (18%) harbored mutations in the HNF-1alpha/MODY3 gene, including a previously unreported change (R271G). One family (4%) carried a novel mutation in the HNF-4alpha gene (IVS5-2delA), representing the first report of a MODY1 pedigree in the Spanish population. The age at diagnosis was prepubertal in MODY2 index patients and pubertal in MODY3 patients. Overt diabetes was rare in MODY2 and was invariably present in MODY3 index patients. Chronic complications of diabetes were absent in the MODY2 population and were present in more than 40% of all relatives of MODY3. Birth weight was lower in the presence of a GCK fetal mutation when the mutation was of paternal origin. The MODY1 patient was diagnosed at 15 yr of age. She developed intermittent microalbuminuria despite good metabolic control, and severe late-onset complications were common within her family. Mutations in the GCK/MODY2 gene are the most common cause of MODY in our population as recruited from pediatric and adolescent index patients. The inheritance of GCK defects by the fetus results in a reduction of birth weight. Clinical expression of MODY3 and MODY1 mutations, the second and third groups of defects found, was more severe, including the frequent development of chronic complications.

Adolescent↗
PubMedDate not supplied

Maturity-onset diabetes of the young (MODY): three case reports and new perspectives.

Maturity-onset diabetes of the young (MODY) is a rare form of juvenile diabetes mellitus that presents with hyperglycaemia in the absence of ketosis. We present three cases of MODY, all of whom had pedigrees with diabetics in multiple generations. All our patients presented in adolescence with evidence of insulin resistance. Two patients were relatively overweight. All three patients were readily controlled on diet alone. None had any clinical evidence of diabetic complications in early adulthood. Recently there has been a marked increase in our understanding of MODY. Genetic linkage and mutational analyses have identified three subtypes (MODY1, 2 and 3) that are all transmitted in an autosomal dominant fashion. The pathophysiology of the MODY subtypes is variable with both increased and decreased insulin levels being seen. A failure to recognise MODY will result in a lack of appropriate therapy and the potential for diabetic complications.

Blood Glucose↗