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Alexis Elias Malavazos Endocrinology Unit, Clinical Nutrition and Cardiovascular Prevention Service, IRCCS Policlinico San Donato, San Donato Milanese, Italy
Department of Biomedical, Surgical and Dental Sciences, Università degli Studi di Milano, Milan, Italy

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Chiara Meregalli Endocrinology Unit, Clinical Nutrition and Cardiovascular Prevention Service, IRCCS Policlinico San Donato, San Donato Milanese, Italy

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Fabio Sorrentino Endocrinology Unit, Clinical Nutrition and Cardiovascular Prevention Service, IRCCS Policlinico San Donato, San Donato Milanese, Italy

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Andrea Vignati Endocrinology Unit, Clinical Nutrition and Cardiovascular Prevention Service, IRCCS Policlinico San Donato, San Donato Milanese, Italy

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Carola Dubini Endocrinology Unit, Clinical Nutrition and Cardiovascular Prevention Service, IRCCS Policlinico San Donato, San Donato Milanese, Italy

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Valentina Scravaglieri Endocrinology Unit, Clinical Nutrition and Cardiovascular Prevention Service, IRCCS Policlinico San Donato, San Donato Milanese, Italy

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Sara Basilico Endocrinology Unit, Clinical Nutrition and Cardiovascular Prevention Service, IRCCS Policlinico San Donato, San Donato Milanese, Italy

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Federico Boniardi Endocrinology Unit, Clinical Nutrition and Cardiovascular Prevention Service, IRCCS Policlinico San Donato, San Donato Milanese, Italy

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Pietro Spagnolo Unit of Radiology, IRCCS Policlinico San Donato, San Donato Milanese, Italy

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Piergiorgio Malagoli Unit of Dermatology, IRCCS Policlinico San Donato, San Donato Milanese, Italy

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Paolo Romanelli Department of Dermatology and Cutaneous Surgery, University of Miami Miller School of Medicine, Miami, Florida, USA

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Francesco Secchi Unit of Radiology, IRCCS Policlinico San Donato, San Donato Milanese, Italy
Department of Biomedical Sciences for Health, Università degli Studi di Milano, Milan, Italy

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Gianluca Iacobellis Department of Medicine, Division of Endocrinology, Diabetes and Metabolism, University of Miami, Florida, USA

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Summary

Psoriasis is often associated with abdominal obesity and type-2 diabetes (T2D). The inflammatory process in psoriasis can target adipose tissue depots, especially those surrounding the heart and coronary arteries, exposing to an increased risk of cardiovascular diseases. A 50-year-old female patient referred to us for abdominal obesity and T2D, which were not controlled with lifestyle modifications. She had suffered from psoriasis for some years and was treated with guselkumab, without success. Epicardial adipose tissue (EAT) attenuation and pericoronary adipose tissue (PCAT) attenuation for each coronary, defined as mean attenuation expressed in Hounsfield unit (HU), were assessed by routine coronary computed tomography angiography. At baseline, EAT attenuation was −80 HU and PCAT attenuation of the right coronary artery (RCA) was −68 HU, values associated with an increased cardiac mortality risk. Psoriasis area and severity index (PASI) was 12.0, indicating severe psoriasis, while dermatology life quality index (DLQI) was 20, indicating a negative effect on the patient’s life. Semaglutide (starting with 0.25 mg/week for 4 weeks, increased to 0.50 mg/week for 16 weeks, and then to 1 mg/week) was started. After 10 months, semaglutide treatment normalized glycated hemoglobin and induced weight loss, particularly at abdominal level, also followed by a reduction in computed tomography-measured EAT volume. EAT attenuation and PCAT attenuation of RCA decreased, showing an important reduction of 17.5 and 5.9% respectively, compared with baseline. PASI and DLQI decreased by 98.3 and 95% respectively, indicating an improvement in psoriasis skin lesions and an important amelioration of the patient’s quality of life, compared with baseline.

Learning points

  • Psoriasis patients affected by obesity and type-2 diabetes (T2D) are often resistant to biologic therapies.

  • Psoriasis is often associated with abdominal obesity, T2D, and cardiovascular diseases (CVD), given their shared inflammatory properties and pathogenic similarities.

  • Epicardial adipose tissue (EAT) inflammation can cause the distinctive pattern of CVD seen in psoriasis.

  • EAT and pericoronary adipose tissue (PCAT) attenuation, assessed by routine coronary computed tomography angiography (CCTA), can be used as biomarkers of inflammation and allow monitoring of medical anti-inflammatory therapies.

  • The actions of semaglutide to reduce energy intake, improve glycemic control, and produce effective weight loss, particularly at the visceral fat depot level, can diminish adipose tissue dysfunction, reduce EAT attenuation and PCAT attenuation of the right coronary artery (RCA) and concomitantly ameliorate the clinical severity of psoriasis.

  • Semaglutide therapy may be considered in psoriasis patients affected by T2D and abdominal obesity, despite low cardiovascular risk by traditional risk scores, who are resistant to biologic therapies.

Open access
Benthe A M Dijkman Department of Endocrinology and Metabolism, Amsterdam UMC location Vrije Universiteit Amsterdam, De Boelelaan 1117, Amsterdam, the Netherlands

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Christel J M de Blok Department of Endocrinology and Metabolism, Amsterdam UMC location Vrije Universiteit Amsterdam, De Boelelaan 1117, Amsterdam, the Netherlands

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Koen M A Dreijerink Department of Endocrinology and Metabolism, Amsterdam UMC location Vrije Universiteit Amsterdam, De Boelelaan 1117, Amsterdam, the Netherlands

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Martin den Heijer Department of Endocrinology and Metabolism, Amsterdam UMC location Vrije Universiteit Amsterdam, De Boelelaan 1117, Amsterdam, the Netherlands

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Summary

A 31-year-old woman with complete androgen insensitivity syndrome (CAIS) experienced breast volume fluctuations during biphasic hormone replacement therapy consisting of estradiol and cyclical dydrogesterone, a progestin. 3D breast volume measurements showed a 100 cc volume (17%) difference between estradiol monotherapy and combined estradiol and dydrogesterone treatment. Progestogen-dependent breast volume changes have not been reported in the literature. Our findings suggest a correlation between progestogen use and breast volume. Due to the rapid cyclical changes, we hypothesize that the effect is caused by fluid retention.

Learning points

  • There is limited reports available on the effects of progesterone on breast development and volume.

  • 3D imaging provides an easy-to-use method to quantify breast volume.

  • The patient in our case description clearly showed that cyclic progesterone use might induce substantial cyclic changes in breast volume.

  • In women with complete androgen insensitivity syndrome (CAIS), monotherapy with estrogen or continuous supplementation of progesterone might be preferable over cyclic progesterone use.

Open access
Livia Lugarinho Correa Department of Obesity, Instituto Estadual de Diabetes e Endocrinologia Luiz Capriglione (IEDE), Rio de Janeiro, Brazil

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Priscila Alves Medeiros de Sousa Department of Obesity, Instituto Estadual de Diabetes e Endocrinologia Luiz Capriglione (IEDE), Rio de Janeiro, Brazil

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Leticia Dinis Department of Obesity, Instituto Estadual de Diabetes e Endocrinologia Luiz Capriglione (IEDE), Rio de Janeiro, Brazil

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Luana Barboza Carloto Department of Obesity, Instituto Estadual de Diabetes e Endocrinologia Luiz Capriglione (IEDE), Rio de Janeiro, Brazil

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Maitane Nuñez-Garcia Pronokal® Group, Barcelona, Spain

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Ignacio Sajoux Pronokal® Group, Barcelona, Spain

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Sidney Senhorini Betaclínica-Centro de Diabetes de Maringá, Paraná, Brazil

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Summary

There is a close association between obesity and type 2 diabetes (T2D). The value of weight loss in the management of patients with T2D has long been known. Loss of 15% or more of body weight can have a disease-modifying effect in people with diabetes inducing remission in a large proportion of patients. Very low-carbohydrate ketogenic diets (VLCKDs) have been proposed as an appealing nutritional strategy for obesity management. The diet was shown to result in significant weight loss in the short, intermediate, and long terms and improvement in body composition parameters as well as glycemic and lipid profiles. The reported case is a 35-year-old man with obesity, dyslipidemia, and T2D for 5 years. Despite the use of five antidiabetic medications, including insulin, HbA1c was 10.1%. A VLCKD through a commercial multidisciplinary weight loss program (PnK method) was prescribed and all medications were discontinued. The method is based on high-biological-value protein preparations and has 5 steps, the first 3 steps (active stage) consist of a VLCKD (600–800 kcal/d) that is low in carbohydrates (<50 g daily from vegetables) and lipids. The amount of proteins ranged between 0.8 and 1.2 g/kg of ideal body weight. After only 3 months, the patient lost 20 kg with weight normalization and diabetes remission, and after 2 years of follow-up, the patient remained without the pathologies. Due to the rapid and significant weight loss, VLCKD emerges as a useful tool in T2D remission in patients with obesity.

Learning points

  • Obesity and type 2 diabetes (T2D) are conditions that share key pathophysiological mechanisms.

  • Loss of 15% or more of body weight can have a disease-modifying effect in people with T2D inducing remission in a large proportion of patients.

  • Diabetes remission should be defined as a return of HbA1c to <6.5% and which persists for at least 3 months in the absence of usual glucose-lowering pharmacotherapy.

  • The very low-carbohydrate ketogenic diet (VLCKD) is a nutritional approach that has significant beneficial effects on anthropometric and metabolic parameters.

  • Due to the rapid and significant weight loss, VLCKD emerges as a useful tool in T2D remission in patients with obesity.

Open access
Carolina Chaves Department of Endocrinology and Nutrition, Hospital Divino Espírito Santo de Ponta Delgada, EPER, Azores Islands, Portugal

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Teresa Kay Department of Medical Genetics, Hospital Dona Estefânia, Centro Hospitalar de Lisboa Central, EPE, Lisbon, Portugal

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João Anselmo Department of Endocrinology and Nutrition, Hospital Divino Espírito Santo de Ponta Delgada, EPER, Azores Islands, Portugal

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Summary

Leptin is secreted by adipocytes in response to fat storage and binds to its receptor (LEPR), which is ubiquitously expressed throughout the body. Leptin regulates energy expenditure and is anorexigenic. In this study, we describe the clinical and hormonal findings of three siblings with a personal history of rapid weight gain during the first months of life. They had delayed puberty, high levels of FSH (15.6 ± 3.7 mUI/mL; reference: 1.5–12.4) and LH (12.3 ± 2.2 mUI/mL; reference: 1.7–8.6), normal oestradiol and total testosterone and successful fertility. None of the patients had dyslipidemia, diabetes or thyroid disease. Next-generation sequencing identified a pathogenic homozygous variant c.2357T>C, p.(Leu786Pro) in LEPR. Their parents and children were heterozygous for this mutation. We compared clinical and biochemical findings of homozygous carriers with first-degree heterozygous family members and ten randomly selected patients with adult-onset morbid obesity. Homozygous carriers of the mutation had significantly higher BMI (32.2 ± 1.7 kg/m2 vs 44.5 ± 7.1 kg/m2, P = 0.023) and increased serum levels of leptin (26.3 ± 9.3 ng/mL vs 80 ± 36.4 ng/mL, P = 0.028) than their heterozygous relatives. Compared with the ten patients with adult-onset morbid obesity, serum levels of leptin were not significantly higher in homozygous carriers (53.8 ± 24.1 ng/mL vs 80 ± 36.4 ng/mL, P = 0.149), and thus serum levels of leptin were not a useful discriminative marker of LEPR mutations. We described a rare three-generation family with monogenic obesity due to a mutation in LEPR. Patients with early onset obesity should be considered for genetic screening, as the identification of mutations may allow personalized treatment options (e.g. MC4R-agonists) and targeted successful weight loss.

Learning points

  • The early diagnosis of monogenic forms of obesity can be of great interest since new treatments for these conditions are becoming available.

  • Since BMI and leptin levels in patients with leptin receptor mutations are not significantly different from those found in randomly selected morbid obese patients, a careful medical history is mandatory to suspect this condition.

  • Loss of leptin receptor function has been associated with infertility. However, our patients were able to conceive, emphasizing the need for genetic counselling in affected patients with this condition.

Open access
Ana Dugic Department for Gastroenterology, Endocrinology and Metabolic Diseases, Bayreuth University Hospital, Friedrich-Alexander University Erlangen-Nuremberg, Bayreuth, Germany

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Michael Kryk Department for Gastroenterology, Endocrinology and Metabolic Diseases, Bayreuth University Hospital, Friedrich-Alexander University Erlangen-Nuremberg, Bayreuth, Germany

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Claudia Mellenthin Department of Surgery, HFR Fribourg, Fribourg, Switzerland

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Christoph Braig Department for Gastroenterology, Endocrinology and Metabolic Diseases, Bayreuth University Hospital, Friedrich-Alexander University Erlangen-Nuremberg, Bayreuth, Germany

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Lorenzo Catanese Department for Nephrology, Angiology and Rheumatology, Bayreuth University Hospital, Friedrich-Alexander University Erlangen-Nuremberg, Bayreuth, Germany

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Sandy Petermann Department for Gastroenterology, Endocrinology and Metabolic Diseases, Bayreuth University Hospital, Friedrich-Alexander University Erlangen-Nuremberg, Bayreuth, Germany

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Jürgen Kothmann Department for Nephrology, Angiology and Rheumatology, Bayreuth University Hospital, Friedrich-Alexander University Erlangen-Nuremberg, Bayreuth, Germany

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Steffen Mühldorfer Department for Gastroenterology, Endocrinology and Metabolic Diseases, Bayreuth University Hospital, Friedrich-Alexander University Erlangen-Nuremberg, Bayreuth, Germany

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Summary

Drinking fruit juice is an increasingly popular health trend, as it is widely perceived as a source of vitamins and nutrients. However, high fructose load in fruit beverages can have harmful metabolic effects. When consumed in high amounts, fructose is linked with hypertriglyceridemia, fatty liver and insulin resistance. We present an unusual case of a patient with severe asymptomatic hypertriglyceridemia (triglycerides of 9182 mg/dL) and newly diagnosed type 2 diabetes mellitus, who reported a daily intake of 15 L of fruit juice over several weeks before presentation. The patient was referred to our emergency department with blood glucose of 527 mg/dL and glycated hemoglobin (HbA1c) of 17.3%. Interestingly, features of diabetic ketoacidosis or hyperosmolar hyperglycemic state were absent. The patient was overweight with an otherwise unremarkable physical exam. Lipase levels, liver function tests and inflammatory markers were closely monitored and remained unremarkable. The initial therapeutic approach included i.v. volume resuscitation, insulin and heparin. Additionally, plasmapheresis was performed to prevent potentially fatal complications of hypertriglyceridemia. The patient was counseled on balanced nutrition and detrimental effects of fruit beverages. He was discharged home 6 days after admission. At a 2-week follow-up visit, his triglyceride level was 419 mg/dL, total cholesterol was 221 mg/dL and HbA1c was 12.7%. The present case highlights the role of fructose overconsumption as a contributory factor for severe hypertriglyceridemia in a patient with newly diagnosed diabetes. We discuss metabolic effects of uncontrolled fructose ingestion, as well as the interplay of primary and secondary factors, in the pathogenesis of hypertriglyceridemia accompanied by diabetes.

Learning points

  • Excessive dietary fructose intake can exacerbate hypertriglyceridemia in patients with underlying type 2 diabetes mellitus (T2DM) and absence of diabetic ketoacidosis or hyperosmolar hyperglycemic state.

  • When consumed in large amounts, fructose is considered a highly lipogenic nutrient linked with postprandial hypertriglyceridemia and de novo hepatic lipogenesis (DNL).

  • Severe lipemia (triglyceride plasma level > 9000 mg/dL) could be asymptomatic and not necessarily complicated by acute pancreatitis, although lipase levels should be closely monitored.

  • Plasmapheresis is an effective adjunct treatment option for rapid lowering of high serum lipids, which is paramount to prevent acute complications of severe hypertriglyceridemia.

Open access
Punith Kempegowda Institute of Metabolism and Systems Research, University of Birmingham, Birmingham, UK
University Hospitals Birmingham NHS Foundation Trust Birmingham, Birmingham, UK

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Wentin Chen Medical School, College of Medical and Dental Sciences, University of Birmingham, Birmingham, UK

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Eka Melson Institute of Metabolism and Systems Research, University of Birmingham, Birmingham, UK
University Hospitals Birmingham NHS Foundation Trust Birmingham, Birmingham, UK

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Annabelle Leong Health Education England West Midlands, Birmingham, UK

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Prashant Amrelia University Hospitals Birmingham NHS Foundation Trust Birmingham, Birmingham, UK

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Ateeq Syed University Hospitals Birmingham NHS Foundation Trust Birmingham, Birmingham, UK

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Summary

A 37-year-old female of South Asian origin was referred to our diabetes clinic for evaluation of an unusual finding during her retinal screening. Her retinal blood vessels appeared white in contrast to the normal pink-red colour. She had type I hyperlipidaemia, confirmed by genotype, and was recently diagnosed with diabetes, secondary to pancreatic insufficiency, for which she had suboptimal control and multiple hospitalisations with recurrent pancreatitis. On examination, she had multiple naevi on her skin; the rest of the examination was unremarkable. The patient did not report any visual disturbances and had intact visual acuity. Investigations showed raised total cholesterol (12.5 mmol/L) and triglycerides (57.7 mmol/L). Following evaluation, the patient was diagnosed with lipaemia retinalis, secondary to type I hyperlipidaemia. The patient was managed conservatively to reduce the cholesterol and triglyceride burdens. However, therapies with orlistat, statin, fibrates and cholestyramine failed. Only a prudent diet, omega-3 fish oil, medium-chain triglycerides oil and glycaemic control optimised with insulin showed some improvements in her lipid profile. Unfortunately, this led her to becoming fat-soluble vitamin deficient; hence, she was treated with appropriate supplementation. She was also recently started on treatment with volanesorsen. Following this, her lipid parameters improved and lipaemia retinalis resolved.

Learning points

  • Lipaemia retinalis is an uncommon incidental finding of type I hyperlipidaemia that may not affect vision.

  • Management of associated dyslipidaemia is challenging with minimal response to conventional treatment.

  • Increased awareness of lipaemia retinalis and specialist management is needed as part of regular patient monitoring and personalised management.

Open access
Priya Darshani Chhiba University of the Witwatersrand, Wits Donald Gordon Medical Centre, Johannesburg, South Africa

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David Segal University of the Witwatersrand, Wits Donald Gordon Medical Centre, Johannesburg, South Africa

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Summary

Recombinant human growth hormone therapy (rhGH) has been available since 1985 for a variety of conditions and has expanded the indications for rhGH therapy and the number of patients receiving therapy. The very nature of the therapy exposes individuals to years of injections. There are a number of well-known adverse events, however, a lesser-known and rarely reported adverse event of rhGH therapy is localized lipoatrophy. We report nine cases of localized lipoatrophy during rhGH therapy accounting for 14.5% of patients taking rhGH presenting to a single centre for routine follow-up over just a 2-month period. The development of localized lipoatrophy does not appear to be age, indication or dose-related but rather related to repeated administration of rhGH into a limited number of sites. The most likely putative mechanism is the local lipolytic action of growth hormone (GH) itself, although the possibility of an excipient-based interaction cannot be excluded. Given the high prevalence of this adverse event and the potential to prevent it with adequate site rotation, we can recommend that patients be informed of the possible development of localized lipoatrophy. Doctors and nurses should closely examine injection sites at each visit, and site rotation should be emphasized during injection technique education.

Learning points

  • There are a number of well-known adverse events, however, a lesser-known and rarely reported adverse event of rhGH therapy is localized lipoatrophy.

  • Examination of the injection sites at each visit by the treating healthcare practitioner.

  • To advise the parents/caregivers/patients to change their injection site with each injection.

  • To advise the parents/caregivers/patients to change the needles after every use.

  • For parents, caregivers and patients to self-inspect their injection sites and have a high alert for the development of lipoatrophy and to then immediately report it to their doctor.

Open access
Fiona Melzer Institute of Diabetes and Clinical Metabolic Research, Kiel, Germany

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Corinna Geisler Institute of Diabetes and Clinical Metabolic Research, Kiel, Germany

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Dominik M Schulte Institute of Diabetes and Clinical Metabolic Research, Kiel, Germany
Department of Medicine 1, Division of Endocrinology, Diabetes and Clinical Nutrition, University Hospital of Schleswig-Holstein, Kiel, Germany

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Matthias Laudes Institute of Diabetes and Clinical Metabolic Research, Kiel, Germany
Department of Medicine 1, Division of Endocrinology, Diabetes and Clinical Nutrition, University Hospital of Schleswig-Holstein, Kiel, Germany

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Summary

Familial partial lipodystrophy (FPLD) syndromes are rare heterogeneous disorders especially in women characterized by selective loss of adipose tissue, reduced leptin levels and severe metabolic abnormalities. Here we report a 34-year-old female with a novel heterozygotic c.485 thymine>guanine (T>G) missense variant (p.phenylalanine162cysteine; (Phe162Cys)) in exon 4 of the peroxisome proliferator-activated receptor gamma (PPARG) gene, developing a non-ketotic diabetes and severe hypertriglyceridemia with triglyceride concentrations >50 mmol/L. In this case, a particular interesting feature in comparison to other known PPARG mutations in FPLD is that while glycaemic control could be achieved through standard anti-diabetic medication, hypertriglyceridemia did neither respond to fibrate nor to omega-3-fatty acid therapy. This might suggest a lipid metabolism driven phenotype of the novel PPARG c.485T>G missense variant. Notably, recombinant leptin replacement therapy (metreleptin (Myalepta®)) was initiated showing a rapid and profound effect on triglyceride levels as well as on liver function tests and satiety feeling. Unfortunately, severe allergic skin reactions developed at the side of injection which could be covered by anti-histaminc treatment. We conclude that the heterozygous PPARG c.485T>G variant is a yet undescribed molecular basis underlying FPLD with difficulties predominantly to control hypertriglyceridemia and that recombinant leptin therapy may be effective in affected subjects.

Learning points

  • Heterozygous c.485T>G variant in PPARG is most likely a cause for FPLD in humans.

  • This variant results in a special metabolic phenotype with a predominant dysregulation of triglyceride metabolism not responding to standard lipid lowering therapy.

  • Recombinant leptin therapy is effective in rapidly improving hypertriglyceridemia.

Open access
Ulla Kampmann Steno Diabetes Center Aarhus, Aarhus University Hospital, Hedeager, Aarhus N, Denmark

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Per Glud Ovesen Department of Obstetrics and Gynecology, Department of Diabetes and Endocrinology, Aarhus University Hospital, Palle Juul Jensens Boulevard, Aarhus N, Denmark

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Niels Møller Medical Research Laboratories, Department of Diabetes and Endocrinology, Aarhus University Hospital, Palle Juul Jensens Boulevard, Aarhus N, Denmark

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Jens Fuglsang Department of Obstetrics and Gynecology, Department of Diabetes and Endocrinology, Aarhus University Hospital, Palle Juul Jensens Boulevard, Aarhus N, Denmark

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Summary

During pregnancy, maternal tissues become increasingly insensitive to insulin in order to liberate nutritional supply to the growing fetus, but occasionally insulin resistance in pregnancy becomes severe and the treatment challenging. We report a rare and clinically difficult case of extreme insulin resistance with daily insulin requirements of 1420 IU/day during pregnancy in an obese 36-year-old woman with type 2 diabetes (T2D) and polycystic ovary syndrome (PCOS). The woman was referred to the outpatient clinic at gestational week 12 + 2 with a hemoglobin A1c (HbA1c) at 59 mmol/mol. Insulin treatment was initiated immediately using Novomix 30, and the doses were progressively increased, peaking at 1420 units/day at week 34 + 4. At week 35 + 0, there was an abrupt fall in insulin requirements, but with no signs of placental insufficiency. At week 36 + 1 a, healthy baby with no hypoglycemia was delivered by cesarean section. Blood samples were taken late in pregnancy to search for causes of extreme insulin resistance and showed high levels of C-peptide, proinsulin, insulin-like growth factor (IGF-1), mannan-binding-lectin (MBL) and leptin. CRP was mildly elevated, but otherwise, levels of inflammatory markers were normal. Insulin antibodies were undetectable, and no mutations in the insulin receptor (INSR) gene were found. The explanation for the severe insulin resistance, in this case, can be ascribed to PCOS, obesity, profound weight gain, hyperleptinemia and inactivity. This is the first case of extreme insulin resistance during pregnancy, with insulin requirements close to 1500 IU/day with a successful outcome, illustrating the importance of a close interdisciplinary collaboration between patient, obstetricians and endocrinologists.

Learning points

  • This is the first case of extreme insulin resistance during pregnancy, with insulin requirements of up to 1420 IU/day with a successful outcome without significant fetal macrosomia and hypoglycemia.

  • Obesity, PCOS, T2D and high levels of leptin and IGF-1 are predictors of severe insulin resistance in pregnancy.

  • A close collaboration between patient, obstetricians and endocrinologists is crucial for tailoring the best possible treatment for pregnant women with diabetes, beneficial for both the mother and her child.

Open access
Marina Yukina Endocrinology Research Centre, Moscow, Russia

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Nurana Nuralieva Endocrinology Research Centre, Moscow, Russia

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Ekaterina Sorkina Endocrinology Research Centre, Moscow, Russia

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Ekaterina Troshina Endocrinology Research Centre, Moscow, Russia

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Anatoly Tiulpakov Endocrinology Research Centre, Moscow, Russia

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Zhanna Belaya Endocrinology Research Centre, Moscow, Russia

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Galina Melnichenko Endocrinology Research Centre, Moscow, Russia

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Summary

Lamin A/C (LMNA) gene mutations cause a heterogeneous group of progeroid disorders, including Hutchinson–Gilford progeria syndrome, mandibuloacral dysplasia, atypical progeroid syndrome (APS) and generalized lipodystrophy-associated progeroid syndrome (GLPS). All of those syndromes are associated with some progeroid features, lipodystrophy and metabolic complications but vary differently depending on a particular mutation and even patients carrying the same gene variant are known to have clinical heterogeneity. We report a new 30-year-old female patient from Russia with an APS and generalized lipodystrophy (GL) due to the heterozygous de novo LMNA p.E262K mutation and compare her clinical and metabolic features to those of other described patients with APS. Despite many health issues, short stature, skeletal problems, GL and late diagnosis of APS, our patient seems to be relatively metabolically healthy for her age when compared to previously described patients with APS.

Learning points

  • Atypical progeroid syndromes (APS) are rare and heterogenic with different age of onset and degree of metabolic disorders, which makes this diagnosis very challenging for clinicians and may be missed until the adulthood.

  • The clinical picture of the APS depends on a particular mutation in the LMNA gene, but may vary even between the patients with the same mutation.

  • The APS due to a heterozygous LMNA p.E262K mutation, which we report in this patient, seems to have association with the generalized lipodystrophy, short stature and osteoporosis, but otherwise, it seems to cause relatively mild metabolic complications by the age of 30.

  • The patients with APS and lipodystrophy syndromes require a personalized and multidisciplinary approach, and so they should be referred to highly specialized reference-centres for diagnostics and treatment as early as possible.

  • Because of the high heterogeneity of such a rare disease as APS, every patient’s description is noteworthy for a better understanding of this challenging syndrome, including the analysis of genotype-phenotype correlations.

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