OBJECTIVE Pregnancy has been associated with development and progression of diabetic retinopathy (DR), but incidence of DR remains unclear. We assessed DR progression rate and its predictors during pregnancies in patients with type 1 diabetes. RESEARCH DESIGN AND METHODS We report the retrospective data from pregnancies in patients with type 1 diabetes followed in Lille, France (1997–2015). Eye examination was performed every 3 months or every month in case of severe nonproliferative retinopathy or progression. Progression was defined by DR degradation (≥1 stage of the Early Treatment Diabetic Retinopathy Study [ETDRS] classification); it included DR development and worsening in patients without and with prepregnancy DR, respectively. RESULTS A total of 499 pregnancies in 375 patients were included; prepregnancy retinopathy was present in 30.3%. Progression, development, and worsening rates were 21.8%, 24.4% of those without retinopathy, and 15.9% of those with retinopathy, respectively. Development of sight-threatening retinopathy was rare. Progression mainly occurred in early or midpregnancy. Elevated prepregnancy HbA1c and duration of diabetes ≥10 years were predictors of DR progression. Among pregnancies with prepregnancy DR, continuous subcutaneous insulin infusion (CSII) tended to decrease the risk of DR progression. Among CSII-treated patients, those with prepregnancy DR had a significantly decreased risk of DR progression. Among the 270 pregnancies of women with any DR during pregnancy who returned for a postpartum ophthalmologic examination, the rate of progression was only 4.1% and the rate of regression was 9.3%. CONCLUSIONS This study provides epidemiologic data on progression of retinopathy during pregnancy and will be useful for future guidelines for retinopathy screening.

Unveiling the key pathways underlying postnatal beta-cell proliferation can be instrumental to decipher the mechanisms of beta-cell mass plasticity to increased physiological demand of insulin during weight gain and pregnancy. Using transcriptome and global Serine Threonine Kinase activity (STK) analyses of islets from newborn (10 days old) and adult rats, we found that highly proliferative neonatal rat islet cells display a substantially elevated activity of the mitogen activated protein 3 kinase 12, also called dual leucine zipper-bearing kinase (Dlk). As a key upstream component of the c-Jun amino terminal kinase (Jnk) pathway, Dlk overexpression was associated with increased Jnk3 activity and was mainly localized in the beta-cell cytoplasm. We provide the evidence that Dlk associates with and activates Jnk3, and that this cascade stimulates the expression of Ccnd1 and Ccnd2, two essential cyclins controlling postnatal beta-cell replication. Silencing of Dlk or of Jnk3 in neonatal islet cells dramatically hampered primary beta-cell replication and the expression of the two cyclins. Moreover, the expression of Dlk, Jnk3, Ccnd1 and Ccnd2 was induced in high replicative islet beta cells from ob/ob mice during weight gain, and from pregnant female rats. In human islets from non-diabetic obese individuals, DLK expression was also cytoplasmic and the rise of the mRNA level was associated with an increase of JNK3, CCND1 and CCND2 mRNA levels, when compared to islets from lean and obese patients with diabetes. In conclusion, we find that activation of Jnk3 signalling by Dlk could be a key mechanism for adapting islet beta-cell mass during postnatal development and weight gain. Keywords Beta-cell mass • Mapk • Obesity • Pregnancy • Postnatal development Abbreviations Ccnd Cyclin D Cdk Cyclin-dependent kinase Cdkn Cyclin-dependent kinase inhibitor DLK Dual leucine Zipper Kinase JNK C-Jun amino terminal kinase MAP3K12 Mitogen-activated protein kinase 12 MAPK10 Mitogen-activated protein kinase 10 STK Serine threonine kinase

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Context Despite optimization of metabolic balance during pregnancy in type 1 diabetes (T1D), maternal-fetal complications remain higher than in the background population. We examined whether there is an association between HbA1c levels and these complications. Methods Retrospective study of pregnancies in 678 T1D subjects at Lille Hospital (1997-2019). The association between variations in HbA1c levels and complications was examined. The composite criterion (CC) was defined as having at least one of the following complications: prematurity, preeclampsia, Large for Gestational Age (LGA), Small for Gestational Age (SGA) or cesarean section. Results Among the 678 births, median pre-conception HbA1c was 7.2% (55mmol/mol), 361 were LGA (56%), 29 were SGA (4.5%) and 504 were births without preterm delivery (76.1%). The CC occurred in 81.8%. Higher HbA1c during the first trimester was associated with the CC (Odds-ratio (OR), 1.04 [95% confidence interval (CI), 1.02 to 1.06] per 0.1% increase; p<0.001). Higher HbA1c during the third trimester was associated with the CC (OR, 1.07 [95% CI, 1.03 to 1.10] per 0.1% increase; p<0.001). The group defined by an 1 st trimester Hba1c > 6.5% (48 mmol/mol) and a 3 rd trimester HbA1c <6% was associated with an increased rate of the CC (OR, 2.81 [95% CI, 1.01 to 7.86]) and an increased rate of LGA (OR, 2.20 [95% CI, 1.01 to 4.78]). Conclusion Elevated HbA1c is associated with maternal fetal complications. Despite optimization of metabolic balance during the 3rd trimester, for patients with early glycemic imbalance the risk of LGA persists.

In contrast to obesity, which is very frequent, lipomatosis and lipodystrophy syndromes are rare diseases of adipose tissue. Lipodystrophy syndromes are characterized by metabolic abnormalities associated with partial or generalized lipoatrophy. Lipomatosis is defined by the presence of several body lipomas without lipoatrophy. Dercum’s disease (DD) and Roch-Leri mesosomatous lipomatosis (RLML) are rare and poorly characterized forms of lipomatosis. They have raised little clinical interest despite the non-negligible consequences of DD on quality of life. The main clinical presentation of these diseases includes multiple lipomas, which are painful in DD (in contrast to RLML). The two diseases are frequently associated with obesity and metabolic syndrome, with hypertension, diabetes, or dyslipidemia. The long-term course of the diseases remains poorly described. DD affects mainly women, whereas RLML mostly affects men. In both diseases lipomas are found on the back and thighs, as well as on the abdomen in DD and the forearms in RLML. The painful lipomas tend to recur after surgery in DD (in contrast to RLML). Most cases are sporadic. No specific treatment has been identified, as the pathophysiology remains unknown. Nevertheless, low-grade fat inflammation and specific abnormalities such as hyperbasophilia deserve further investigation. The aim of this review is to analyze the available literature on the topic.

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