DIABETES COMPLICATIONS

  CUPRINS:
Alphabetical list of authors XI

Short presentation XXI

1. Metabolically healthy vs. unhealthy obesity phenotypes: The PREDATORR Survey (M. Mota, S. G. Popa, E. Mota, PREDATORR Study Group, Romania) 1

2. Role of advanced glycation endproducts in the development of diabetic complications (A. Stirban, Neuss, Germany) 19

3. HbA1c and diabetic complications (D. Cheta, E. Rusu, C. Stanciu, C. Pena, Bucharest, Romania) 56

4. Impact of individual deprivation on diabetic complications (H. Bihan, R. Cohen, H. Le Clesiau, L. Charra, C. Burnot, M. Fysekidis, E. Cosson, I. Tauveron, Clermont-Ferrand, Paris, France) 65

5. From Obesity to Diabetes: Could inflammation be the link (M. Batisse-Lignier, S. Maqdasy, B. Roche, E. Pastel, A.-M. Lefrancois-Martinez, I. Tauveron, Clermont-Ferrand, France) 82

6. Infections and diabetes mellitus (E. Dumea, R. Miulescu Danciulescu, Constanta, Bucharest, Romania) 109

7. Bivalent cations and complications of diabetes mellitus (M. Nechifor, C. Gales, C. Zamfir, Iasi, Romania) 122

8. Pancreatic Islet Amyloid Polypeptide (IAPP or Amylin) and type 2 diabetes (E. Ganea, Bucharest, Romania) 137

9. Peculiarities of silent myocardial ischemia in diabetic patients (S. Maqdasy, M. Batisse-Lignier, F. Desbiez, B. Catargi, I. Tauveron, Clermont-Ferrand, France) 154

10. Insulin, the brain and diabetes complications (C. D. Popescu, M. Graur, C. Grosu, B. E. Ignat, D. Alexa, Iasi, Romania) 180

11. Diabetes and stroke (E. V. Bacanu, Bucharest, Romania) 207

12. Genetic factors in the pathogenesis of diabetic kidney disease. An update (C. Guja, L. Guja, C. Ionescu-Tirgoviste, Bucharest, Romania) 255

13. The chronic kidney disease in diabetes mellitus patients. An update (C. Serafinceanu, Bucharest, Romania) 292

14. The ketodiet - a challenging mean in the treatment of the renal chronic diabetic disease (I. Teodoru, Bucharest, Romania) 305

15. Diabetic eye disease (D. Catrinoiu, V. Coviltir, I. R. Parepa, L. Mazilu, Constanta, Bucharest, Romania) 326

16. Diabetic neuropathy. New insights with a focus on oxidative stress (O. Savu, Bucharest, Romania) 353

17. Diabetic neuropathy. Investigations and current treatment options (C. Constantin, S. Ivan, D. Cheta, Bucharest, Romania) 366

18. Diabetic cardiovascular autonomic neuropathy (M. Ursache, O. A. Parliteanu, A. Dumitrescu, Bucharest, Romania) 384

19. Erectile dysfunction in diabetic patients (G. F. Dale, L. M. Popa, A. R. Popa, Oradea, Romania) 409

20. New insights into the management of Charcot osteoartropathy (V. Elian, E. Catrina, I. Japie, M. Sandulescu, Bucharest, Romania) 426

21. Diabetic foot ulcers (L. C. Nwabudike, Bucharest, Romania) 440

22. Prognostic criteria during pregnancy in women with preexisting diabetes (type 1 and type 2) (I. Ceausu, D. A. Mihai, Bucharest, Romania) 463

23. Gestational diabetes. An update (D. A. Mihai, I. Ceausu, Bucharest, Romania) 500

24. Diabetes mellitus and obstructive sleep apnea (M. Graur, D. Boisteanu, O. Nita, L. I. Arhire,
L. Mihalache, Iasi, Romania) 528

25. Asthma and diabetes mellitus (C. Radu, F. de Blay, Strasbourg, France) 557

26. Chronic pulmonary obstructive disease and diabetes (E. Rusu, G. Radulian, Bucharest, Romania) 577

27. Bariatric surgery in remission of diabetes mellitus and its complications (C. Zetu, Bucharest, Romania) 599

28. Diabetes, obesity and cancer: a deadly association (S. Ioacara, Bucharest, Romania) 623

29. Non-alcoholic steatohepatitis (NASH). An underrecognized, underdiagnosed and undertreated complication of diabetes: current trends and future developments (B. Balas, Basel, Switzerland) 634

Selected list of previous books (D. Cheta, Bucharest, Romania) 661
  PREZENTARE:
At the beginning of this book the results of the so called “The Predatorr Survey”, a Romanian epidemiological study, are commented. This survey indicates a high prevalence of metabolically healthy obese phenotype and a better overall metabolic profile in metabolically healthy obese individuals than that observed in lean and obese subjects with metabolic syndrome. The metabolically healthy phenotype may be the key to understanding the mechanisms that link obesity to cardiovascular and metabolic risk. Thus, it seems to be important to stratify obesity based on the metabolic phenotype in order to identify the subjects which need to be prioritized for early pharmacological therapy besides lifestyle optimisation (Chap. 1).

The enhanced generation and accumulation of advanced glycation endproducts (AGEs) have been linked to increased risk for vascular complications in diabetes. AGEs result from the nonenzymatic reaction of reducing sugars with proteins, lipids and nucleic acids potentially altering their function by disrupting molecular conformation, promoting crosslinking, altering enzyme activity, reducing their clearance and impairing receptor recognition. AGEs may also activate specific receptors, like the receptor for AGEs (RAGE), which is present on the surface of all cells relevant to vascular disease and diabetes complications, triggering oxidative stress, inflammation and apoptosis. Understanding the pathogenic mechanisms of AGEs is paramount for the development of therapeutic strategies (Chap. 2).

The most interesting connections between HbA1c and chronic complications of diabetes are evaluated. Several studies concluded that risk of vascular complications in diabetes begins to increase at an HbA1c level of 6.5%. In the Framingham Heart Study, one percentage point elevation in HbA1c was correlated with a 1.39 - fold increased risk of cardiovascular disease. Elevated HbA1c is independently related to cardiovascular disease even in subjects without a diabetes diagnosis (Chap. 3).

Individual deprivation, although not frequently explored in daily practice or epidemiological studies, can be an important risk factor for diabetic incidence, micro- and macrovascular complications. Nevertheless, concerns remain as to whether the management of diabetic patients of low socioeconomic status is different from that of a privileged patient, and how we can close this gap (Chap. 4).

Obesity increases the risk of developing type 2 diabetes. Adipose tissue dysfunction belongs to the primary defects in obesity and may link obesity to several health problems including increased risk of type 2 diabetes and cardiovascular disease. Impaired adipose tissue function contributes to a proinflammatory, atherogenic, and diabetogenic state (Chap. 5).

Host susceptibility factors contributing to increased risk of bacterial infections in diabetes will undoubtedly be multifactorial depending on tissue tropism, the type of protective immune response required and the unique life cycles of various pathogens. We are only beginning to understand the molecular mechanisms underline susceptibility (Chap. 6).

The levels of plasma and cell concentrations of bivalent cations (Magnesium, Zinc, Copper, Calcium, Chromium, Manganese, Vanadium, Iron) are important markers for the risk of development of diabetes complications (Chap. 7).

Islet amyloid polypeptide (IAPP) or Amylin is the most important constituent of amyloid deposits, characteristic for type 2 diabetes. The human IAPP (hIAPP) is a 37-residue amyloidogenic peptide hormone secreted with insulin simultaneously by pancreatic beta-cells in the islets of Langerhans. Considering that hIAPP undergoes conformational modifications from soluble peptide to aggregation and tisular deposit, T2DM was accepted as a member of the conformational diseases family. As a consequence we paid a special attention to the relation between IAPP and T2DM, as a conformational disease (Chap. 8).

Coronary complications related to diabetes directly affect life expectancy, turning this vast pathology into a major public health problem. Silent myocardial ischemia (SMI) is relatively frequent in diabetic patients and commonly underestimated. Taken together, at least one fifth of diabetic patients suffer from these silent episodes, which are considered the “alarm bell” alerting to a possible, more severe, coronary artery disease, where a prompt control of cardiovascular risk factors prevents further evolution (Chap. 9).

In the context of rapidly increasing evidence that diabetes can have a critical role in different neurological disorders, many brain studies establish an association of diabetes to neurodegenerative and vascular brain pathology.

When patients have a long history of diabetes (especially if they are getting old), have cognitive complaints, unexplained poor metabolic control, or if cognitive and behavioral changes are reported by an informant, it is useful to search for cognitive decline. The patient may then be referred to a memory clinic for a work-up including brain imaging, to identify the cause of this decline leading to appropriate medical and socio-medical management (Chap. 10).

Diabetes Mellitus is a strong and independent risk factor for ischaemic cerebrovascular disease with a relative risk of around two compared to nondiabetic patients. Ischaemic stroke in the patient with diabetes has worse outcomes, including a higher rate of mortality than in patients without diabetes, one of six patients with diabetes dies from stroke. The patients with diabetes is predisposed to vascular events, including ischaemic cerebrovascular disease and stroke for a number of reasons such as premature atherosclerosis, reduced response to nitric oxide and a general state of hypercoagulability. Prevention of stroke in the patient with diabetes is best accomplished through aggressive management of coexisting hypertension and hyperlipidemia as well as lifestyle modification. Diabetes is common amongst patients with stroke and is associated with poorer outcomes. Reduction of glycated hemoglobin as a proxy for good glycaemic control is likely to be associated with reduction of macrovascular events. Many basic scientific works have sugested that hyperglycaemia documented in the early stages of stroke is associated with worse outcomes and aggressive management of hyperglycaemia in the acute stroke period may improve prognosis (Chap. 11).

Classic candidate gene studies and modern genome wide scanning approaches have identified a number of putative diabetic kidney disease (DKD) loci. However, there are still important gaps in our knowledge of the genetic architecture of DKD and there is the need to speed up research in this field, especially addressing the issue of the variation in multiple ethnic groups and diverse disease phenotypes. Overall, unravelling the genetic basis of DKD could contribute to the elucidation of the precise molecular basis of this condition and pave the way towards early detection and development of novel therapeutic strategies. This could finally contribute to a decrease in the incidence of DKD with the associated benefits in reduced morbidity and mortality (Chap. 12).

Chronic kidney disease (CKD) associated with diabetes mellitus (DM), mainly with type 2, is still the leading cause of end stage renal disease (ESRD) in USA and Western Europe and an increasing trend is being registered worldwide. Type 2 DM and arterial hypertension separately or together account for about 75% of the new ESRD patients initiated on renal replacement therapies in 2011 in USA. However, in the last few years a new classification for CKD has been proposed by KDIGO resulting from the conclusions of some recent trials and this is enforcing, in our opinion, a change in the current paradigm of the diabetic kidney disease (DKD) (Chap. 13).

Ketodiet seems to be a promising nutritional tool in the therapeutic approach, even in diabetic patients with advanced CKD and nephrotic syndrome, in selected patients without severe gastrointestinal disturbances or other severe catabolic conditions and acidosis, mandatory sustained nutritional assistance, according to their energetic needs and comorbidities and with adequate psychological advice, suited to their personality profiles (Chap. 14).

Diabetic eye disease remains one of the major causes of vision loss in the western world. Only 35-50% of patients with diabetes mellitus receive regular eye examinations, which are important for timely diagnosis and proper treatment. The necessary goals are better patient education to improve the control of diabetes and better screening programs to reduce the risk of blindness from diabetic retinopathy. Therefore, greater emphasis must be placed on preventing complications, which will require both a better understanding of the mechanisms by which diabetes affects the retina and an improved means of detecting retinopathy (Chap. 15).

Exacerbated mitochondrial ROS production under chronic hyperglycemia and hypoxia as the main characteristics of the diabetic milieu is nowadays considered essential for the progression of specific chronic complications of diabetes, including neuropathy. Increased oxidative stress in diabetes may be also associated with a significant decrease in the efficiency of the antioxidant defense, especially in long-term exposure to hyperglycemia. However, targeting oxidative stress alone in diabetes may be insufficient to completely understand the complex pathogenic panel of specific chronic complications or to alleviate their devastating clinical impact (Chap. 16).

Diabetic neuropathy is a chronic microvascular complication in both type 1 and type 2 Diabetes, having an important contribution to increased morbidity and mortality for these patients. The severity of neuropathy has been related with the long term of poor glycemic control by numerous studies.

Though, the heterogeneity of clinical presentations cannot be explained only by a few risk factors (age, disease duration, glycemic control); additional cardiovascular factors have recently been elucidated. This situation had led to the need to develop new diagnostic procedures and neurological tests in order to differentiate between dysfunctions of different nerve fibers correlated with similar clinical patterns (Chap. 17).

Cardiovascular autonomic neuropathy (CAN) has been established as a major complication of diabetes with significant negative impact on survival and quality of life in people with diabetes. It is an important cause of morbidity and mortality associated with a high risk of cardiac arrhythmias and sudden death. CAN is defined as the impairment of autonomic control of the cardiovascular system in the setting of diabetes after exclusion of other causes. CAN is associated with resting tachycardia, postural hypotension, painless myocardial ischemia or infarction, arrhythmias and sudden cardiac death (Chap. 18).

The general impact of erectile dysfunction (ED) on the quality of life of men of all ages and their partners should not be underestimated. ED can decrease the will to initiate sexual relations because of the fear and humility associated with a weak sexual performance therefore a prompt line of investigations and the correct treatment must be initiated as soon as possible all the while taking a sensitive approach to the patient`s needs (Chap. 19).

Charcot neuropathic osteoarthropathy of the foot and ankle (Charcot foot) is a syndrome characterized by an acute localized inflammatory condition that may lead to varying degrees and patterns of bone destruction, subluxation, dislocation, and deformity due to the interaction of several component factors (diabetes, sensorimotor neuropathy, autonomic neuropathy, trauma and metabolic abnormalities of bone). The impact of Charcot arthropathy on morbidity and mortality, as well as the costs of hospitalization and treatment are of great importance, especially in the onset of acute episodes, thus early diagnosis and prevention are top priorities in the management of this condition (Chap. 20).

Diabetic foot ulcers (DFU) are an important source of morbidity and mortality. A large number of treatment modalities already exist. Some are “ancient”, but still prove to be effective. Others are new and there is limited evidence regarding their efficacy as well as cost-effectiveness in many cases. These deficits need to be addressed by large studies that will improve physician knowledge in this regard and therefore inform more efficacious care. The care of patients with DFU demands a holistic, multidisciplinary approach (Chap. 21).

Diabetes in pregnancy may preexist pregnancy (pregestational), or may be diagnosed during pregnancy, after the first trimester (gestational diabetes). Pregestational diabetes may be type 1 or type 2 diabetes and, generally, the pregnancy is associated with increased risk of both maternal and neonatal complications. Pregestational type 1 and 2 diabetes can affect fertility, it can cause obstetric, fetal and neonatal complications, affecting the entire period of pregnancy. Moreover, it may predispose the offspring to increased risk of obesity and diabetes. The mother is also at increased risk of diabetes-related complications (especially retinopathy, nephropathy or worsening of these complications if they were already present) (Chap. 22).

Today, it is clear that identifying of gestational diabetes mellitus (GDM) overpasses the medical discussion of utility, both for the mother and child, both for the short term and long term possible complications. It is a fact that diagnosis can be done only in pregnancy and this is an ethical problem. GDM is a common complication in pregnancy, and its prevalence varies with the different approaches used to screen and diagnose it, but the overall prevalence is approximately around 7% of all pregnancies. Besides the test employed to diagnose the race, ethnicity, age and body composition influences the prevalence of GDM, which may range from 1 to 14%. As is observed in general for diabetes mellitus, multiple prevalence studies reported increases in prevalence of GDM during the last 20 years (Chap. 23).

By definition, sleep apnea is the clinical entity which presents as abnormal breathing during sleep. In particular, obstructive sleep apnea syndrome is defined by repeated episodes of complete or partial obstruction of the upper airway during sleep, associated with loud snoring and daytime sleepiness, which, incidentally, all three together, are the cardinal symptoms of apnea. Obesity is the most common risk factor for this disorder and it is recognized as the most important one, along with other diseases with which obesity and OSA are associated and/or has causality, i.e. type 2 diabetes, prediabetes, dyslipidemia, metabolic syndrome and hypertension (Chap. 24).

Asthma, diabetes and obesity are frequent and complex diseases whose prevalence is increasing, particularly among young people. We still have a long and winding road ahead until all mechanisms behind the development of asthma and diabetes have been unraveled. Until then, the possible relationships and potential up- or down-regulative interactions between asthma and diabetes should be observed with caution (Chap. 25).

Chronic obstructive pulmonary disease (COPD) and diabetes mellitus (DM) are common and underdiagnosed medical conditions whose prevalence is increasing. It is predicted that COPD will be the third leading cause of death worldwide by 2020. On the other hand, diabetes may act as an independent factor negatively affecting lung structure and function.

Prospective population-based and experimental evidence is needed to elucidate the crucial pathways between COPD, insulin resistance, and DM (Chap. 26).

It is well documented that T2DM remission occurs after bariatric surgery. The precise nature of the diabetic remission through surgery has not been completely elucidated. It is likely that a combination of a calorierestricted diet, gastrointestinal and adipose hormonal changes, and weight loss result in an early and long-lasting remission for T2DM. Furthermore, it would be important for the patient to undergo the operation while still in the early stages of T2DM to increase the chance to obtaining complete remission. Thus, bariatric surgery should be considered a part of standard therapy for T2DM, but only a proportion of eligible diabetic patients undergo bariatric surgery (Chap. 27).

The link between diabetes, obesity and cancer risk is explained by a complex interplay between deranged levels of insulin resistance, insulin, IGF1, inflammatory markers, adipokines, and sex hormones. Diabetes medication seems to finally modulate these interactions, raising either hopes or concerns about cancer-related outcomes. Intensive research is being undertaken on this topic and hopefully we will soon be able to have better knowledge about the best strategies to both prevent and eventually treat obesity- and diabetes-related cancers (Chap. 28).

Non-alcoholic fatty liver disease (NAFLD) and non-alcoholic steatohepatitis (NASH) are conditions with potentially severe outcomes. The presence of obesity, insulin resistance and diabetes are major factors associated with an increased risk of progression to NASH, end-stage liver failure and hepatocellular carcinoma. Lifestyle intervention remains the cornerstone of treatment in NAFLD/NASH but it is difficult to achieve and maintain. Thus far, vitamin E and TZDs are the most promising pharmacological therapies (Chap. 29).
  PREFATA:
A large volume (VASCULAR INVOLVEMENT IN DIABETES: Clinical, Experimental and Beyond - Edited by Dan Cheta - Editura Academiei Romane, Bucuresti and S.Karger AG, Basel, Switzerland) was published in 2005. Meanwhile the medical and social impact of diabetes and its complications dramatically increased. A new book dedicated to this topic seems necessary.

Basically, the objectives of such a work would be: a high scientific level, an elegant design and commercial attractiveness. A large group of distinguished authors was recruited from Romania, France, Germany and Switzerland. The cooperation with the Printing House
was fruitful.

We are much indebted to all the contributors and friends.

Professor of Medicine
Dan Mircea CHETA, MD, PhD
Bucharest, June 2014

ALPHABETICAL LIST OF AUTHORS:

Daniel ALEXA, MD
“Grigore T.Popa” University of Medicine and Pharmacy, Iasi, Romania

Lidia Iuliana ARHIRE, MD, PhD
„Grigore T.Popa” University of Medicine and Pharmacy, Iasi, Romania

Elena Violeta BACANU, MD, PhD
“N. Paulescu” National Institute of Diabetes, Nutrition and Metabolic Diseases, Bucharest, Romania
Email: drelena_bac@yahoo.com

Bogdan BALAS, MD
F. Hoffmann-La Roche AG
Basel, Switzerland
E-mail: bogdan.balas@roche.com

Marie BATISSE-LIGNIER, MD, PhD student
Praticien Hospitalier
Service Endocrinologie-Diabetologie, CHU G. Montpied,
58 rue Montalembert, F63000
Clermont-Ferrand, France
Genetique, Reproduction et Developpement (GreD),
CNRS UMR6293-INSERM U1103
Clermont Universite, F63170 Aubiere, France

Helene BIHAN, MD, PhD
MCUPH
Department of Endocrinology, Diabetology, Metabolic Disease, AP-HP,
Avicenne Hospital
Senior Physician
UMR U557 INSERM/U11125 INRA/CNAM/Paris 13 University,
Sorbonne Paris Cite,
CRNH-IdF, Bobigny, France
E-mail: helene.bihan@avc.aphp.fr

Daniela BOISTEANU, MD, PhD
Associate Professor
„Grigore T.Popa” University of Medicine and Pharmacy, Iasi, Romania

Christelle BURNOT, MD
Service Endocrinologie-Diabetologie, CHU G. Montpied,
58 rue Montalembert, F63000
Clermont-Ferrand, France
E-mail: cburnot@chu-clermontferrand.fr

Bogdan CATARGI, MD, PhD
Professor of Medicine
Service d’Endocrinologie-Diabetologie,
CHU F33000 Bordeaux, France
E-mail : bogdan.catargi@chu-bordeaux.fr

Eduard CATRINA, MD, PhD
Senior Lecturer
“Carol Davila” University of Medicine and Pharmacy, Bucharest, Romania
E-mail: eduardcatrina@yahoo.com

Doina CATRINOIU, MD, PhD
Professor of Medicine
“Ovidius” University Constanta, Romania
E-mail: dcatrinoiu@gmail.com

Iuliana CEAUSU, MD, MSc, PhD
Senior Lecturer in Obstetrics and Gynecology,
“Carol Davila” University of Medicine and Pharmacy, Bucharest, Romania
Head of the Department of Obstetrics and Gynecology II, “Dr. I. Cantacuzino” Clinical Hospital, Bucharest, Romania
E-mail: iulianaceausu2004@yahoo.com

Laurene CHARRA, MD
Service Endocrinologie-Diabetologie, CHU G. Montpied,
58 rue Montalembert, F63000
Clermont-Ferrand, France
E-mail: lcharra@chu-clermontferrand.fr

Dan Mircea CHETA, MD, PhD
Professor of Medicine
“N. Paulescu” National Institute of Diabetes, Nutrition and Metabolic Diseases, Bucharest, Romania
E-mail: chetadan@gmail.com

Regis COHEN, MD, PhD
Department of Diabetology, Delafontaine Hospital,
Senior Physician
Saint-Denis, France
E-mail : regis.cohen@ch-stdenis.fr

Alex-George CIOBLA, MD
The Emergency Eye Hospital, Bucharest, Romania

Ciprian CONSTANTIN, MD, PhD
“Dr. Carol Davila” University Central Military Emergency Hospital,
Bucharest, Romania
E-mail: ciprian_constantin@yahoo.com

Emmanuel COSSON, MD, PhD
Department of Endocrinology-Diabetology-Nutrition,
AP-HP, Jean Verdier Hospital,
Senior Physician
UMR U557 INSERM/U11125 INRA/CNAM/Paris 13 University,
Sorbonne, Paris Cite,
CRNH-IdF, Bobigny, France
E-mail: emmanuel.cosson@jvr.aphp.fr

Valeria COVILTIR, MD, PhD
“Carol Davila” University of Medicine and Pharmacy, Bucharest, Romania
E-mail: valeriacoviltir@yahoo.com

Gabriela Florina DALE, MD, PhD student
Emergency Clinical County Hospital, Oradea, Romania
E-mail: gabriela_dale@yahoo.com

Rucsandra MIULESCU DANCIULESCU, MD, PhD
Senior Lecturer
“Carol Davila” University of Medicine and Pharmacy, Bucharest, Romania
E-mail: rucsandra_m@yahoo.com

Frederic DE BLAY, MD, PhD
Professor of Medicine
University of Strasbourg, France
E-mail: frederic.deblay@chru-strasbourg.fr

Françoise DESBIEZ, MD
Service Endocrinologie-Diabetologie, CHU G. Montpied,
58 rue Montalembert, F63000
Clermont-Ferrand, France
E-mail: fdesbiez@chu-clermontferrand.fr

Elena DUMEA, MD, PhD
Assistant Professor
“Ovidius” University Constanta, Romania
E-mail: elenadumea@yahoo.com

Adriana DUMITRESCU, MD
Sanamed Hospital, Bucharest, Romania
E-mail: medicaldiab@yahoo.com

Viviana ELIAN, MD, PhD
Assistant Professor
“Carol Davila” University of Medicine and Pharmacy, Bucharest, Romania
“N. Paulescu” National Institute of Diabetes, Nutrition and Metabolic Diseases,
Bucharest, Romania
E-mail: vivelian@yahoo.com

Marinos FYSEKIDIS, MD, PhD student
Department of Endocrinology, Diabetology, Metabolic Disease, AP-HP,
Avicenne Hospital
Senior Physician
UMR U557 INSERM/U11125 INRA/CNAM/Paris 13 University,
Sorbonne Paris Cite,
CRNH-IdF, Bobigny, France
E-mail: marinos.fysekidis@jvr.aphp.fr

Cristina GALES, MD
“Grigore T. Popa” University of Medicine and
Pharmacy, Department of Histology, Iasi, Romania

Elena GANEA, MD, PhD
Associate Professor
Head of “Protein Folding” Department
Institute of Biochemistry, Romanian Academy 296
Splaiul Independentei 060031
Bucharest Romania
E-mail: emaganea@gmail.com

Mariana GRAUR, MD, PhD
Professor of Medicine
“Grigore T.Popa” University of Medicine and Pharmacy, Iasi, Romania
E-mail: graur.mariana@gmail.com

Cristina GROSU, MD, PhD
“Grigore T.Popa” University of Medicine and Pharmacy, Iasi, Romania

Cristian GUJA, MD, PhD
Associate Professor
“Carol Davila” University of Medicine and Pharmacy, Bucharest, Romania
“N. Paulescu” National Institute of Diabetes, Nutrition and Metabolic Diseases, Bucharest, Romania
Email: cristian.guja@b.astral.ro

Loreta GUJA, MD, PhD
“Lotus” Medical Center, Bucharest, Romania

Bogdan Emilian IGNAT, MD, PhD
“Grigore T. Popa” University of Medicine and Pharmacy, Iasi, Romania

Sorin IOACARA, MD, PhD
Asistant Professor
“Carol Davila” University of Medicine and Pharmacy, Bucharest, Romania
E-mail: drsorin@yahoo.com

Constantin IONESCU-TIRGOVISTE, MD, PhD
Professor of Medicine
“N. Paulescu” National Institute of Diabetes, Nutrition and Metabolic Diseases, Bucharest, Romania

Sanda IVAN, MD
“N. Paulescu” National Institute of Diabetes, Nutrition and Metabolic Diseases, Bucharest, Romania
E-mail: dr.sandaivan@yahoo.ro

Ionut JAPIE, MD
Emergency University Hospital Bucharest, Romania
E-mail: ionutjapie@yahoo.com

Herve LE CLESIAU, MD
Centre d’Examens de Sante de la Caisse Primaire d’Assurance Maladie de Seine-Saint-Denis, Bobigny, France
Senior Physician
Director
E-mail: herve.le-clesiau@cpam-bobigny.cnamts.fr

Anne Marie LEFRANCOIS-MARTINEZ, PhD
Professor at University Blaise Pascal
Genetique, Reproduction et Developpement (GreD),
CNRS UMR6293-INSERM U1103
Clermont Universite, F63170 Aubiere, France
E-mail : a-marie.lefrancois-martinez@univ-bpclermont.fr

Salwan MAQDASY, MD, PhD student
Service Endocrinologie-Diabetologie, CHU G. Montpied,
58 rue Montalembert, F63000
Clermont-Ferrand, France
Genetique, Reproduction et Developpement (GreD),
CNRS UMR6293-INSERM U1103
Clermont Universite, F63170 Aubiere, France
E-mail : smaqdasy@chu-clermontferrand.fr

Anne Marie LEFRANCOIS-MARTINEZ, MD
Genetique, Reproduction et Developpement (GreD), CNRS UMR6293-INSERM
U1103-Clermont Universites, F63170, France

Laura MAZILU, MD, PhD
“Ovidius” University, Constanta, Romania
E-mail: lauragrigorov@gmail.com

Doina Andrada MIHAI, MD, PhD student
“Carol Davila” University of Medicine and Pharmacy, Bucharest, Romania
“N. Paulescu” National Institute of Diabetes, Nutrition and Metabolic Diseases, Bucharest, Romania

Laura MIHALACHE, MD, PhD
„Grigore T.Popa” University of Medicine and Pharmacy, Iasi, Romania

Maria Cristina MOGOS, MD
The emergency Eye Hospital, Bucharest, Romania

Maria MOTA, MD, PhD
Professor of Medicine
University of Medicine and Pharmacy Craiova, Romania
E-mail: mmota53@yahoo.com

Eugen MOTA, MD, PhD
Professor of Medicine
University of Medicine and Pharmacy Craiova, Romania

Mihai NECHIFOR, MD, PhD
Professor of Medicine
“Grigore T. Popa” University of Medicine and Pharmacy, Iasi, Romania
E-mail: mnechif@yahoo.com

Otilia NITA, MD, PhD
„Grigore T.Popa” University of Medicine and Pharmacy, Iasi, Romania

Lawrence Chuckwudi NWABUDIKE, MD, PhD
“N. Paulescu” National Institute of Diabetes, Nutrition and Metabolic Diseases, Bucharest, Romania
E-mail: chukwudi.nwabudike@live.com

Irinel-Raluca PAREPA, MD, PhD
“Ovidius” University Constanta, Romania
E-mail: irinel_parepa@yahoo.com

Oana-Andreea PARLITEANU, MD, PhD student
Sanamed Hospital, Bucharest, Romania
E-mail: oana_andreea@yahoo.com

Emilie PASTEL, PhD student
Genetique, Reproduction et Developpement (GreD),
CNRS UMR6293-INSERM U1103
Clermont Universite, F63170 Aubiere, France
E-mail : Emilie.PASTEL1@univ-bpclermont.fr

Cosmin PENA, MD
“N. Paulescu” National Institute of Diabetes, Nutrition and Metabolic Diseases, Bucharest, Romania
E-mail: cosmin76pena@yahoo.com

Simona Georgiana POPA, MD, PhD
Assistant Professor
University of Medicine and Pharmacy Craiova, Romania

Loredana Madalina POPA, MD, PhD student
Emergency Clinical County Hospital, Oradea, Romania
E-mail: popa_lori2000@yahoo.com

Amorin Remus POPA, MD, PhD
Professor of Medicine
Faculty of Medicine and Pharmacy Oradea, Romania
E-mail: popa_amorin@yahoo.com

Cristian Dinu POPESCU, MD, PhD
Professor of Medicine
“Grigore T.Popa” University of Medicine and Pharmacy, Iasi, Romania

Carmen RADU, MD
University of Strasbourg, France
E-mail: carmen.radu@chru-strasbourg.fr

Gabriela RADULIAN, MD, PhD
Professor of Medicine
“Carol Davila” University of Medicine and Pharmacy, Bucharest, Romania
E-mail: gradulian@umf.ro

Beatrice ROCHE, MD
Praticien Hospitalier
Service Endocrinologie-Diabetologie, CHU G. Montpied,
58 rue Montalembert, F63000
Clermont-Ferrand, France
E-mail:b__roche@chu-clermontferrand.fr

Emilia RUSU, MD, PhD
Assistant Professor
“Carol Davila” University of Medicine and Pharmacy, Bucharest, Romania
E-mail: emiliarusumd@yahoo.com

Mihai SANDULESCU, MD
National Institute of Aerospace Medicine, Bucharest, Romania
E-mail: mihail-escu@yahoo.com

Octavian SAVU, MD, PhD
“N. Paulescu” National Institute of Diabetes, Nutrition and Metabolic Diseases, Bucharest, Romania
E-mail: savu.octavian@gmail.com

Cristian SERAFINCEANU, MD, PhD
Associate Professor
“N. Paulescu” National Institute of Diabetes, Nutrition and Metabolic Diseases, Bucharest, Romania
E-mail: cristianserafinceanu@yahoo.com

Cristian STANCIU, MD
“N. Paulescu” National Institute of Diabetes, Nutrition and Metabolic Diseases, Bucharest, Romania
E-mail: drstanciu@gmail.com

Alin STIRBAN, MD, PhD
Director Endocrinology and Diabetes Complications
Profil, Hellersbergstr. 9, 41460 Neuss, Germany
Email: alin.stirban@profil.com
Address for correspondence:
Alin Stirban, Director Endocrinology and Diabetes Complications,
Profil Institut fur Stoffwechselforschung, Hellersbergstr. 9, 41460 Neuss, Germany
Tel: +49-2131-4018-486, Fax: +49-2131-4018-500, E-mail: alin.stirban@profil.com

Igor TAUVERON, MD, PhD
Professor at Universite d’Auvergne
Service Endocrinologie-Diabetologie, CHU G. Montpied,
58 rue Montalembert, F63000
Clermont-Ferrand, France
Genetique, Reproduction et Developpement (GreD),
CNRS UMR6293-INSERM U1103
Clermont Universite, F63170 Aubiere, France
Email: itauveron@chu-clermontferrand.fr

Ileana TEODORU, MD, PhD student
“N. Paulescu” National Institute of Diabetes, Nutrition and Metabolic Diseases, Bucharest, Romania
E-mail: teodoruileana@yahoo.com

Mihaela URSACHE, MD, PhD student
Sanamed Hospital, Bucharest, Romania
E-mail: ursachemiha@yahoo.com

Carmen ZAMFIR, MD, PhD
Professor of Medicine
“Grigore T. Popa” University of Medicine and Pharmacy, Iasi, Romania

Cornelia ZETU, MD, PhD student
“N. Paulescu” National Institute of Diabetes, Nutrition and Metabolic Diseases, Bucharest, Romania
E-mail: corapnc@yahoo.com
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