Dipeptidyl Peptidase-IV Inhibitors Are Efficient Adjunct Therapy in <i>HNF1A</i> Maturity-Onset Diabetes of the Young Patients—Report of Two Cases

Katra, Barbara; Klupa, Tomasz; Skupień, Jan; Szopa, Magdalena; Nowak, Natalia; Borowiec, Maciej; Kozek, Elżbieta; Małecki, Maciej T.

doi:10.1089/dia.2009.0159

Cited by 32 publications

(22 citation statements)

References 12 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…The findings in our trial are, however, consistent with recent case studies reporting beneficial effects of dipeptidyl peptidase-4 inhibitors in patients with HNF1A diabetes when combined with other oral glucose-lowering drugs (14,15) or with liraglutide as adjunct therapy to SU and basal insulin (16). Whether monotherapy with GLP-1RA is sufficiently effective to maintain an acceptable long-term glycemic regulation in patients with HNF1A diabetes is not clear from our trial.…”

Section: 028supporting

confidence: 79%

“…In 2006, Tuomi et al (11) demonstrated that during physical exercise in patients with HNF1A diabetes (light cycling for 30 min approximately 2 h after ingesting a meal), hypoglycemia was observed in 40% of subjects treated with an SU (glibenclamide); one patient experienced hypoglycemia for 12 h. In contrast to the glucose-independent insulinotropic effect of SUs, GLP-1 receptor agonists (GLP-1RAs) exert an insulinotropic effect in a strictly glucose-dependent manner, with no effect at PG concentrations ,4-5 mmol/L (12,13), translating into a low risk of hypoglycemia. Therefore, GLP-1RA treatment might be safe and efficacious for patients with HNF1A diabetes, but so far only a few cases have been reported (14)(15)(16).…”

mentioning

confidence: 99%

See 1 more Smart Citation

Glucose-Lowering Effects and Low Risk of Hypoglycemia in Patients With Maturity-Onset Diabetes of the Young When Treated With a GLP-1 Receptor Agonist: A Double-Blind, Randomized, Crossover Trial

et al. 2014

View full text Add to dashboard Cite

OBJECTIVEThe most common form of maturity-onset diabetes of the young (MODY), hepatocyte nuclear factor 1a (HNF1A diabetes: MODY3) is often treated with sulfonylureas that confer a high risk of hypoglycemia. We evaluated treatment with GLP-1 receptor agonists (GLP-1RAs) in patients with HNF1A diabetes. RESEARCH DESIGN AND METHODSSixteen patients with HNF1A diabetes (8 women; mean age 39 years [range 23-67 years]; BMI 24.9 6 0.5 kg/m 2 [mean 6 SEM]; fasting plasma glucose [FPG] 9.9 6 0.9 mmol/L; HbA 1c 6.4 6 0.2% [47 6 3 mmol/mol]) received 6 weeks of treatment with a GLP-1RA (liraglutide) and placebo (tablets), as well as a sulfonylurea (glimepiride) and placebo (injections), in randomized order, in a double-blind, crossover trial. Glimepiride was up-titrated once weekly in a treat-to-target manner; liraglutide was up-titrated once weekly to 1.8 mg once daily. At baseline and at the end of each treatment period a standardized liquid meal test was performed, including a 30-min light bicycle test. RESULTSFPG decreased during the treatment periods (21.6 6 0.5 mmol/L liraglutide [P = 0.012] and 22.8 6 0.7 mmol/L glimepiride [P = 0.003]), with no difference between treatments (P = 0.624). Postprandial plasma glucose (PG) responses (total area under the curve) were lower with both glimepiride (2,136 6 292 min 3 mmol/L) and liraglutide (2,624 6 340 min 3 mmol/L) compared with baseline (3,127 6 291 min 3 mmol/L; P < 0.001, glimepiride; P = 0.017, liraglutide), with no difference between treatments (P = 0.121). Eighteen episodes of hypoglycemia (PG £3.9 mmol/L) occurred during glimepiride treatment and one during liraglutide treatment. CONCLUSIONSSix weeks of treatment with glimepiride or liraglutide lowered FPG and postprandial glucose excursions in patients with HNF1A diabetes. The glucose-lowering effect was greater with glimepiride at the expense of a higher risk of exclusively mild hypoglycemia.

show abstract

Section: 028supporting

confidence: 79%

mentioning

confidence: 99%

Glucose-Lowering Effects and Low Risk of Hypoglycemia in Patients With Maturity-Onset Diabetes of the Young When Treated With a GLP-1 Receptor Agonist: A Double-Blind, Randomized, Crossover Trial

et al. 2014

View full text Add to dashboard Cite

show abstract

“…Treatment of patients with MODY using an incretinbased strategy has been described in a few cases (23,24). Our study demonstrates that HNF1A-diabetes shares incretin-related pathophysiology with type 2 diabetes, i.e., reduced incretin effect, which was one of the incentives for incretin-based treatment for type 2 diabetes.…”

Section: Discussionmentioning

confidence: 60%

Incretin Effect and Glucagon Responses to Oral and Intravenous Glucose in Patients With Maturity-Onset Diabetes of the Young—Type 2 and Type 3

et al. 2014

View full text Add to dashboard Cite

Maturity-onset diabetes of the young (MODY) is a clinically and genetically heterogeneous subgroup of nonautoimmune diabetes, constituting 1–2% of all diabetes. Because little is known about incretin function in patients with MODY, we studied the incretin effect and hormone responses to oral and intravenous glucose loads in patients with glucokinase (GCK)-diabetes (MODY2) and hepatocyte nuclear factor 1α (HNF1A)-diabetes (MODY3), respectively, and in matched healthy control subjects. Both MODY groups exhibited glucose intolerance after oral glucose (most pronounced in patients with HNF1A-diabetes), but only patients with HNF1A-diabetes had impaired incretin effect and inappropriate glucagon responses to OGTT. Both groups of patients with diabetes showed normal suppression of glucagon in response to intravenous glucose. Thus, HNF1A-diabetes, similar to type 2 diabetes, is characterized by an impaired incretin effect and inappropriate glucagon responses, whereas incretin effect and glucagon response to oral glucose remain unaffected in GCK-diabetes, reflecting important pathogenetic differences between the two MODY forms.

show abstract

“…Additional data have shown that patients with MODY 3 are more responsive to sulfonylureas than metformin (16 ). Several case reports have suggested that dipeptidyl peptidase-IV inhibitors may further improve blood glucose control when used in combination with sulfonylureas in MODY 3 patients (17,18 ). More studies will be required to confirm these observations and determine whether incretin analogs have similar effects.…”

Section: Monogenic Diabetes Subtypesmentioning

confidence: 99%

Personalized Medicine in Diabetes

Malandrino

Smith

2011

Clinical Chemistry

View full text Add to dashboard Cite

BACKGROUND:Multiple genes that are associated with the risk of developing diabetes or the risk of diabetes complications have been identified by candidate gene analysis and genomewide scanning. These molecular markers, together with clinical data and findings from proteomics, metabolomics, pharmacogenetics, and other methods, lead to a consideration of the extent to which personalized approaches can be applied to the treatment of diabetes mellitus.CONTENT: Known genes that cause monogenic subtypes of diabetes are reviewed, and several examples are discussed in which the genotype of an individual with diabetes can direct considerations of preferred choices for glycemic therapy. The extent of characterization of polygenic determinants of type 1 and type 2 diabetes is summarized, and the potential for using this information in personalized management of glycemia and complications in diabetes is discussed. The application and current limitations of proteomic and metabolomic methods in elucidating diabetes heterogeneity is reviewed.

show abstract

Dipeptidyl Peptidase-IV Inhibitors Are Efficient Adjunct Therapy in HNF1A Maturity-Onset Diabetes of the Young Patients—Report of Two Cases

Abstract: DPP-IV inhibitors may be an effective tool of combined therapy in HNF1A MODY, and they seem to improve beta-cell function under fasting conditions.

Cited by 32 publications

References 12 publications

Glucose-Lowering Effects and Low Risk of Hypoglycemia in Patients With Maturity-Onset Diabetes of the Young When Treated With a GLP-1 Receptor Agonist: A Double-Blind, Randomized, Crossover Trial

Glucose-Lowering Effects and Low Risk of Hypoglycemia in Patients With Maturity-Onset Diabetes of the Young When Treated With a GLP-1 Receptor Agonist: A Double-Blind, Randomized, Crossover Trial

Incretin Effect and Glucagon Responses to Oral and Intravenous Glucose in Patients With Maturity-Onset Diabetes of the Young—Type 2 and Type 3

Personalized Medicine in Diabetes

Contact Info

Product

Resources

About