Case report: management of a young male patient with diabetic ketoacidosis and thyroid storm.

This report describes a case of concomitant diabetic ketoacidosis (DKA) and thyroid storm (TS) in a 20-year-old male patient that presented both diagnostic and management challenges owing to their intricate interrelationship in endocrine-metabolic disorders. The patient, previously diagnosed with type 1 diabetes mellitus (T1DM) and hyperthyroidism, was admitted to the emergency department with symptoms of DKA and progressive exacerbation of TS. Initial treatment focused on correcting DKA; as the disease progressed to TS, it was promptly recognized and treated. This case emphasizes the rarity of simultaneous occurrence of DKA and TS, as well as the challenges in clinical diagnosis posed by the interacting pathophysiological processes and overlapping clinical manifestations of DKA and TS. The patient's treatment process involved multiple disciplines, and after treatment, the patient's critical condition of both endocrine metabolic diseases was alleviated, after which he recovered and was eventually discharged from the hospital. This case report aims to emphasize the need for heightened awareness in patients with complex clinical presentations, stress the possibility of concurrent complications, and underscore the importance of prompt and collaborative treatment strategies.

Periodontitis in patients with diabetes and its association with diabetes-related complications. A register-based cohort study.

OBJECTIVE: To evaluate the association between type 1 diabetes (T1D)/type 2 diabetes (T2D) and periodontitis and assess the influence of periodontitis on diabetes-related complications. DESIGN: Observational study; longitudinal analysis of register data. SETTING: Swedish primary care centres, hospitals and dental clinics reporting to nationwide healthcare registers (2010-2020). PARTICIPANTS: 28 801 individuals with T1D (13 022 women; mean age 42 years) and 57 839 individuals without diabetes (non-T1D; 26 271 women; mean age 43 years). 251 645 individuals with T2D (110 627 women; mean age 61 years) and 539 805 individuals without diabetes (non-T2D; 235 533 women; mean age 60 years). Diabetes and non-diabetes groups were matched for age, gender and county of residence. MAIN OUTCOME MEASURES: Prevalent periodontitis, diabetes-related complications (retinopathy, albuminuria, stroke and ischaemic heart disease) and mortality. RESULTS: Periodontitis was more common among T2D (22%) than non-T2D (17%). Differences were larger in younger age groups (adjusted RR at age 30-39 years 1.92; 95% CI 1.81 to 2.03) and exacerbated by poor glycaemic control. Periodontitis prevalence was 13% in T1D and 11% in non-T1D; only the subgroup with poor glycaemic control was at higher risk for periodontitis. Periodontitis was associated with a higher incidence of retinopathy (T1D: HR 1.08, 95% CI 1.02 to 1.14; T2D: HR 1.08, 95% CI 1.06 to 1.10) and albuminuria (T1D: HR 1.14, 95% CI 1.06 to 1.23; T2D: HR 1.09, 95% CI 1.07 to 1.11). Periodontitis was not associated with a higher risk for stroke, cardiovascular disease or higher mortality in T1D/T2D. CONCLUSIONS: The association between T2D and periodontitis was strong and exacerbated by poor glycaemic control. For T1D, the association to periodontitis was limited to subgroups with poor glycaemic control. Periodontitis contributed to an increased risk for retinopathy and albuminuria in T1D and T2D.

Protein glycation products associate with progression of kidney disease and incident cardiovascular events in individuals with type 1 diabetes.

BACKGROUND: Despite improved glycemic treatment, the impact of glycation on pathological consequences may persist and contribute to adverse clinical outcomes in diabetes. In the present study we investigated the association between serum protein glycation products and progression of kidney disease as well as incident major adverse cardiovascular events (MACE) in type 1 diabetes. METHODS: Fructosamine, advanced glycation end products (AGEs), and methylglyoxal-modified hydro-imidazolone (MG-H1) were measured from baseline serum samples in the FinnDiane study (n = 575). Kidney disease progression was defined as steep eGFR decline (> 3 mL/min/1.73 m2/year) or progression of albuminuria (from lower to higher stage of albuminuria). MACE was defined as acute myocardial infarction, coronary revascularization, cerebrovascular event (stroke), and cardiovascular death. RESULTS: Fructosamine was independently associated with steep eGFR decline (OR 2.15 [95% CI 1.16-4.01], p = 0.016) in the fully adjusted model (age, sex, baseline eGFR). AGEs were associated with steep eGFR decline (OR 1.58 per 1 unit of SD [95% CI 1.07-2.32], p = 0.02), progression to end-stage kidney disease (ESKD) (HR 2.09 per 1 unit of SD [95% CI 1.43-3.05], p < 0.001), and pooled progression (to any stage of albuminuria) (HR 2.72 per 1 unit of SD [95% CI 2.04-3.62], p < 0.001). AGEs (HR 1.57 per 1 unit of SD [95% CI 1.23-2.00], p < 0.001) and MG-H1 (HR 4.99 [95% CI 0.98-25.55], p = 0.054) were associated with incident MACE. MG-H1 was also associated with pooled progression (HR 4.19 [95% CI 1.11-15.89], p = 0.035). Most AGEs and MG-H1 associations were no more significant after adjusting for baseline eGFR. CONCLUSIONS: Overall, these findings suggest that protein glycation products are an important risk factor for target organ damage in type 1 diabetes. The data provide further support to investigate a potential causal role of serum protein glycation in the progression of diabetes complications.

Loss to Follow-Up: Patients with Type 1 Diabetes During the SARS-CoV-2 Pandemic.

The SARS-CoV-2 (severe acute respiratory syndrome related coronavirus 2) pandemic revealed many flaws in our health care system. This review aims to explore the significance of loss to follow-up on patients with type 1 diabetes during the pandemic, the morbidity and mortality associated, and strategies to prevent loss to follow-up or to re-engage patients in longitudinal care. [Pediatr Ann. 2024;53(7):e254-e257.].

COVID-19 and Type 1 Diabetes.

The coronavirus disease 2019 (COVID-19) pandemic brought about several challenges for pediatric patients that were considerably different than those for adult patients. While adult patients had severe illness with associated respiratory and multiorgan failure and subsequent death, pediatric patients typically had milder disease. There were increases in postinfection complications, including an increased incidence of new-onset type 1 diabetes (T1D) following COVID-19 infection, particularly in adolescent patients. Currently, there is increasing concern that COVID-19 infection may be contributing to the development of T1D. This review will provide an overview of COVID-19, T1D, and the increased incidence noted during the pandemic, and the proposed mechanism of development of T1D in this specific patient demographic. Future studies will be needed to understand the long-term impact of the COVID-19 pandemic on T1D in children and adolescents. [Pediatr Ann. 2024;53(7):e244-e248.].

Poor glycemic control impairs oral health in children with type 1 diabetes mellitus - a systematic review and meta-analysis.

OBJECTIVE: There are more than one million children and adolescents living with type 1 diabetes mellitus, and their number is steadily increasing. Diabetes affects oral health through numerous channels, including hyposalivation, immune suppression, and the inflammatory effect of glycation end-products. However, patients with type 1 diabetes must follow a strict sugar free diet that is proven to be carioprotective. Therefore, the aim of this systematic review and meta-analysis is to investigate whether children with type 1 diabetes have a difference in Decayed, Missing, Filled Teeth index (DMFT), salivary function, and periodontal status than children without diabetes, with an emphasis on glycemic control. MATERIALS AND METHODS: PubMed, Embase and Cochrane libraries were screened for articles, using predefined search keys without any language or date restrictions. Two independent authors performed the selection procedure, extracted data from the eligible articles, carried out a manual search of the reference lists, and assessed the risk of bias using the Newcastle-Ottawa scale. Meta-analysis was performed in R using the random-effects model. Effect sizes were mean differences; subgroup analysis was performed on glycemic control. RESULTS: 33 studies satisfied the eligibility criteria. 22 studies did not show a significant difference regarding the DMFT index between the diabetes and non-diabetes groups; six studies found that children living with diabetes had higher DMFT scores, compared to five studies that found significantly lower scores. Meta-analysis found no statistically significant differences in plaque, gingival, and calculus indexes, however it found significant differences in pooled DMFT indexes, and salivary flow rate. Subgroup analysis on glycemic control using DMFT values found significant differences in children with good and poor glycemic control with results of 0.26 (CI95%=-0.50; 1.03) and 1.46 (CI95%=0.57; 2.35), respectively. CONCLUSIONS: Children with poor glycemic control face higher risk of developing caries compared to good control and non-diabetes children. Regular dental check-ups and strict control of glycemic levels are highly advised for children living with type 1 diabetes, further emphasizing the importance of cooperation between dentists and diabetologists.

Eating Disorders and Sleep Disturbance as Determinants of Metabolic Control in Adolescents with Type 1 Diabetes.

This cross-sectional study examined the effect of sleep disturbance and eating disorders on metabolic control in adolescents with Type 1 Diabetes. The study was conducted with adolescents with T1DM treated at a university hospital in Turkey between October 2023 and January 2024. The study sample consisted of 120 adolescents with T1DM between the ages of 10-18. Data were collected online using the Adolescent Information Form, Dutch Eating Behavior Questionnaire (DEBQ), and DSM-5 Sleep Disorder Scale (SDS). Mean, percentage, and regression analyses were used to analyze the data. Ethics committee, institutional permission and written permission from the adolescents with Type 1 Diabetes and their parents were obtained for the study. In the current study, sleep disturbance and eating disorders explained 38.5% and 40.2% of HbA1c, respectively, and were found to have a significant effect (respectively: F = 73.737, p ≤ .001; F = 19.353, p ≤ .001). This study provides evidence that eating disorders and sleep disturbance explain approximately half of HbA1c. The results of the study revealed that sleep disturbance and eating disorders were significant predictors of metabolic control in adolescents with type 1 diabetes.

Insulin resistance may accelerate typical changes in heart function among type 1 diabetes patients, particularly in overweight patients: a preliminary study.

Introduction: Type 1 diabetes (T1D) is a metabolic disease characterized by insulin deficiency and subsequent hyperglycemia. Cardiovascular diseases are the prime cause of mortality and morbidity among patients with T1D. Accumulating metabolic disturbances and accelerated cardiac fibrosis fuel the development of heart dysfunction. As insulin resistance (IR) is a risk factor for the development and worsened course of heart failure, this study aimed to assess its impact on heart function in patients with T1D. Methods: Adult participants were recruited prospectively. The inclusion criteria included a diagnosis of T1D. The exclusion criteria were other types of diabetes, symptoms/treatment of heart failure, AST and/or ALT exceeding the upper reference limit by ≥2x, hepatitis, alcoholism, metformin treatment, and pregnancy. The participants underwent a medical interview, physical examination, biochemical test, and echocardiography. Results: The mean age in the study group was 38 ± 9.6 years, and the mean diabetes duration was 21.8 ± 11.3 years. The median BMI in the study cohort was 23.39 kg/m2. Patients with IR had significantly lower mitral E/A ratio and left ventricular and left atrial volume ratio (LVLAVR), higher LV mass index, and presented with altered mitral annular velocities. Conclusions: IR seems to accelerate the pattern of typical changes in heart function among patients with T1D, especially in the overweight subgroup.

An Observational Study of the Physical and Biochemical Complications and Socioeconomic Status of Type 1 Diabetic Patients in West Bengal, India: A 25-year Follow-up Report of 224 Patients.

BACKGROUND: Limited information is available on the total profile of type 1 diabetes mellitus patients in India. The present study has been undertaken, therefore, in search of socioeconomic status, glycaemic status and the state of complications of the type 1 diabetics attending the diabetic clinic run by Calcutta Diabetes and Endocrine Foundation (CDEF), Kolkata. OBJECTIVES: (1) To obtain the glycemic, socioeconomic, and complications status of type 1 diabetic patients; (2) to see any change of the abovementioned parameters in this follow-up period of 25 years; (3) to take necessary action to improve the quality of care and the health condition of the type 1 diabetics attending the clinic. STUDY DESIGN AND SETTING: A longitudinal observational study. A total of 265 patients were recruited for the study, having been diagnosed or seen within 1 year of diagnosis of type 1 diabetes at the Diabetic Clinic of CDEF. A total of 41 patients were excluded from the study for different reasons, and 224 patients were finally selected. These 224 patients were classified into five separate cohorts according to their first attendance in the diabetes clinic: 1996-2000 (I), 2001-2005 (II), 2006-2010 (III), 2011-2015 (IV), and 2016-2020 (V). Baseline and socioeconomic (based on education and occupational status) data was obtained at the first visit, and mean biochemical parameters were taken from multiple visits. Complications and mortality rates were calculated against the duration of the disease at the end of the study. RESULTS: Gradual improvement of glycemic status was noted when groups I and V were compared. Delayed development of complications and comparatively long life were also observed. CONCLUSION: Several methods of improvement of clinical disease management, including continuous diabetes education with proper training, can improve diabetes care, leading to delays in the development of diabetic complications and ensuring longer as well as healthier life in type 1 diabetes. The development of socioeconomic status might have played some role.

Pregnancy Outcomes in Women with Poorly Controlled Pregestational Diabetes Mellitus.

BACKGROUND: The prevalence of pregestational diabetes mellitus (PGDM) in women of reproductive age has surged globally, contributing to increased rates of adverse pregnancy outcomes. Hemoglobin A1c (HbA1c) is a crucial marker for diagnosing and monitoring PGDM, with periconceptional levels influencing the risk of congenital anomalies and complications. OBJECTIVES: To evaluate the association between periconceptional HbA1c levels and perinatal complications in pregnant women with poorly controlled PGDM. METHODS: We conducted a retrospective analysis of prospectively collected data of pregnancies between 2010 and 2019, HbA1c > 6% at 3 months prior to conception or during the first trimester. Outcomes of periconceptional HbA1c levels were compared. RESULTS: The cohort included 89 women: 49 with HbA1c 6-8%, 29 with HbA1c 8-10%, and 11 with HbA1c > 10%. Higher HbA1c levels were more prevalent in type 1 diabetics and were associated with increased end-organ damage risk. Women with elevated HbA1c levels tended toward unbalanced glucose levels during pregnancy. The cohort exhibited high rates of preterm delivery, hypertensive disorders, cesarean delivery, and neonatal intensive care unit admission. Overall live birth rate was 83%. While a significant correlation was found between HbA1c levels and preterm delivery, no consistent association was observed with other adverse outcomes. CONCLUSIONS: Periconceptional glycemic control in PGDM pregnancies is important. Elevated HbA1c levels are associated with increased risks of adverse outcomes. Beyond a certain HbA1c level, risks of complications may not proportionally escalate.

Is the urinary neutrophil gelatinase-associated lipocalin concentration in children and adolescents with type 1 diabetes mellitus different from that in healthy children?

Introduction: Diabetic kidney disease (DKD) is one of the major microvascular complications of type 1 diabetes mellitus (T1DM). Some studies suggest that changes of renal tubular components emerge before the glomerular lesions thus introducing the concept of diabetic tubulopathy with urinary neutrophil gelatinase-associated lipocalin (uNGAL) as a potential marker of DKD. This concept was not confirmed in all studies. Materials and methods: In 198 T1DM patients with median age 15 years and diabetes duration over one year, an albumin/creatinine ratio (ACR) was determined and uNGAL measured in spot urine sample. Urine samples for ACR and uNGAL were also collected in the control group of 100 healthy children of similar age. Results: There was no significant difference in uNGAL concentration or uNGAL/creatinine between T1DM children and healthy subjects (6.9 (2.8-20.1) ng/mL vs 7.9 (2.9-21.0) ng/mL, P = 0.969 and 6.8 (2.2-18.4) ng/mg vs 6.5 (1.9-13.4) ng/mg, P = 0.448, respectively) or between T1DM subjects with albuminuria A2 and albuminuria A1 (P = 0.573 and 0.595, respectively). Among T1DM patients 168 (85%) had normal uNGAL concentrations, while in 30 (15%) patients uNGAL was above the defined cut-off value of 30.9 ng/mL. There was no difference in BMI, HbA1c and diabetes duration between patients with elevated uNGAL compared to those with normal uNGAL. Conclusions: We found no significant difference in uNGAL concentration or uNGAL/creatinine between T1DM children and healthy subjects or between albuminuria A2 and albuminuria A1 T1DM subjects. Therefore, uNGAL should not be recommended as a single marker for detecting diabetic kidney disease in children and adolescents.

Factors Affecting Mode of Birth in Women With Preexisting Diabetes and Gestational Diabetes: A Retrospective Cohort at a Tertiary Referral Center.

Women with preexisting diabetes and gestational diabetes mellitus (GDM) are at higher risk for adverse maternal and neonatal outcomes. However, there is no consensus on a uniform approach regarding mode of birth (MOB) for all forms of diabetes. The aim of the study is to compare MOB in women with preexisting diabetes and GDM and possible factors influencing it. A retrospective cohort study of women with GDM and preexisting diabetes between 2015 and 2021 at a tertiary referral center was conducted. One thousand three hundred eighty-five singleton pregnancies were included. One thousand twenty-two (74.4%) women had a vaginal birth (VB) and 351 (25.6%) a caesarean section. Preexisting diabetes was significantly associated with caesarean section compared to GDM (OR 2.43). Five hundred fifty-one (40.1%) women underwent induction of labor, and 122 (22.1%) women had a secondary caesarean after IOL. Women induced due to spontaneous rupture of membrane (SROM) achieved the highest rate of VB at 93%. The lowest rates of VB occurred if indication for induction was for preeclampsia or hypertension. IOL was significantly less successful in preexisting diabetes with a VB achieved in 56.4% for type 1 diabetes and 52.6% of type 2 diabetes compared to GDM (78.2% in GDM; 81.2% in IGDM; OR 3.25, 95% CI 1.70-6.19, p < 0.001). The rate of VB was higher who were induced preterm compared to women with term IOL (n = 240 (81.9%) vs. n = 199 (73.2%); p < 0.05). Parity, previous VB and SROM favored VB after IOL, whereas preexisting diabetes, hypertension, and IOL after 40 + 0 weeks are independent risk factors for caesarean delivery.

A Rare Case of Hyperglycemia, Ketoacidosis, and Central Facial Paralysis in a Newly-Diagnosed Diabetic Woman.

BACKGROUND Diabetes mellitus is a chronic disease that occurs when the pancreas does not produce enough insulin or when the body is unable to effectively use the insulin it produces. Uncontrolled diabetes mellitus is usually associated with neurological manifestations, such as hemichorea, focal epileptic seizures, peripheral neuropathy, and peripheral facial paralysis. This report describes a 59-year-old woman presenting with hyperglycemia and ketoacidosis due to newly diagnosed diabetes mellitus, as well as a temporary episode of central facial paralysis, which regressed within a few days after medical treatment and metabolic correction. CASE REPORT A 59-year-old patient with hypertension and a family history of diabetes mellitus presented with polyuro-polydipsic syndrome and signs of metabolic ketoacidosis, with an elevated anion gap, compatible with newly discovered type 1 diabetes mellitus. Six hours after admission, we noted the abrupt onset of left central facial paralysis, with no brain damage shown on magnetic resonance imaging. Initially, the diagnosis was transient ischemic attack. After a second, normal cerebral magnetic resonance image on the fourth day, and clinical improvement on the fifth day after metabolic correction by insulin therapy and rehydration, the diagnosis of a regressive central facial paralysis was retained. CONCLUSIONS Central facial paralysis in diabetic ketoacidosis is a rare neuroendocrine entity. The pathophysiological mechanisms that can explain the occurrence of central facial paralysis are not yet described and require further investigation. This report highlights the importance of diagnosis, early management of hyperglycemia and diabetic ketoacidosis, and reversibility of central facial paralysis after treatment.

Downregulation of hsa-miR-100-5p May Be a Protective Factor in the Early Stages of Nephropathy in Type 1 Diabetes Mellitus.

Type 1 Diabetes Mellitus (T1DM) can generate severe complications, such as Diabetic Kidney Disease (DKD) or Diabetic Nephropathy (DN), with it emerging as the leading cause of terminal (end-stage) renal disease all over the world. For T1DM, the clinical evaluation of DKD uses markers like the Glomerular Filtration Rate (GFR) and the Urinary Albumin Excretion (UAE). However, early diagnosis of DKD is still a challenge. For this reason, investigating molecular markers, such as microRNAs (miRNAs), offers a promising perspective to an early diagnosis, highlighting the stability and the ability to reflect incipient molecular manifestations. Thus, here we investigated four miRNAs (hsa-let-7i-5p, hsa-miR-143-3p, hsa-miR-501-3p, and hsa-miR-100-5p) regarding nephropathy in patients with T1DM, considering the albuminuria (micro and macro) as a standard to evaluate the groups. As a result, we found a reduced expression of miR-100-5p in patients with MIC, indicating a protective role in nephropathy. Beyond that, expression levels between the groups (Non vs. UAE) were not significant when comparing the miRNAs miR-501-3p and miR-143-3p. Finally, miR-143-3p and miR-100-5p were linked to some target genes such as AKT1, MMP13, and IGF1R, that are connected to signal pathways and cellular metabolism.

The association of thyroid autoimmunity with ovarian reserve in women with type 1 diabetes with and without polycystic ovary syndrome.

The aim of the study was to investigate the relation between thyroid autoimmunity (TAI), reflected as the presence of thyroid peroxidase antibodies (TPOAb), and parameters of ovarian reserve in women with type 1 diabetes (T1DM) and polycystic ovary syndrome (PCOS). We studied 83 euthyroid women with T1DM (age - 26 ± 5 years, BMI - 24 ± 3 kg/m2) - 12 with PCOS and positive TPOAb (PCOS + TPOAb), 29 with PCOS with negative TPOAb (PCOS + noTPOAb), 18 without PCOS with positive TPOAb (noPCOS + TPOAb), 24 without PCOS with negative TPOAb (noPCOS + noTPOAb). Serum concentrations of anti-Müllerian hormone (AMH), sex hormones, TSH, thyroid hormones and TPOAb were assessed. The prevalence of TAI was comparable between PCOS and noPCOS. We did not observe differences in hormonal profile or AMH concentration between two PCOS groups-PCOS + TPOAb and PCOS + noTPOAb (p > 0.05). Women with PCOS + TPOAb had lower FSH concentration and higher LH/FSH index than noPCOS + noTPOAb (p = 0.027; p = 0.019, respectively). Moreover, PCOS + TPOAb had lower oestradiol level than noPCOS + TPOAb (p = 0.041). AMH concentration was higher in both groups with PCOS, independent of TPOAb presence, than in noPCOS + noTPOAb (both p < 0.001). The presence of positive TPOAb titre was not related to the studied parameters of ovarian reserve - AMH and ovarian follicle number. In multiple linear regression analysis, the only significant predictor of AMH in the whole studied group with T1DM was total daily insulin dose U/kg (ß = - 0.264; p = 0.022). The presence of TAI did not affect the hormonal profile or ovarian reserve in women with T1DM with and without PCOS.

Multicentre, retrospective cohort study protocol to identify racial and ethnic differences in acute kidney injuries in children and adolescents with diabetic ketoacidosis.

INTRODUCTION: Approximately 40% of children with diabetic ketoacidosis (DKA) develop acute kidney injury (AKI), which increases the risk of chronic kidney damage. At present, there is limited knowledge of racial or ethnic differences in diabetes-related kidney injury in children with diabetes. Understanding whether such differences exist will provide a foundation for addressing disparities in diabetes care that may continue into adulthood. Further, it is currently unclear which children are at risk to develop worsening or sustained DKA-related AKI. The primary aim is to determine whether race and ethnicity are associated with DKA-related AKI. The secondary aim is to determine factors associated with sustained AKI in children with DKA. METHODS AND ANALYSIS: This retrospective, multicentre, cross-sectional study of children with type 1 or type 2 diabetes with DKA will be conducted through the Paediatric Emergency Medicine Collaborative Research Committee. Children aged 2-18 years who were treated in a participating emergency department between 1 January 2020 and 31 December 2023 will be included. Children with non-ketotic hyperglycaemic-hyperosmolar state or who were transferred from an outside facility will be excluded. The relevant predictor is race and ethnicity. The primary outcome is the presence of AKI, defined by Kidney Disease: Improving Global Outcomes criteria. The secondary outcome is 'sustained' AKI, defined as having AKI ≥48 hours, unresolved AKI at last creatinine measurement or need for renal replacement therapy. Statistical inference of the associations between predictors (ie, race and ethnicity) and outcomes (ie, AKI and sustained AKI) will use random effects regression models, accounting for hospital variation and clustering. ETHICS AND DISSEMINATION: The Institutional Review Board of Children's Minnesota approved this study. 12 additional sites have obtained institutional review board approval, and all sites will obtain local approval prior to participation. Results will be presented at local or national conferences and for publication in peer-reviewed journals.

Glycolytic lactate in diabetic kidney disease.

Lactate elevation is a well-characterized biomarker of mitochondrial dysfunction, but its role in diabetic kidney disease (DKD) is not well defined. Urine lactate was measured in patients with type 2 diabetes (T2D) in 3 cohorts (HUNT3, SMART2D, CRIC). Urine and plasma lactate were measured during euglycemic and hyperglycemic clamps in participants with type 1 diabetes (T1D). Patients in the HUNT3 cohort with DKD had elevated urine lactate levels compared with age- and sex-matched controls. In patients in the SMART2D and CRIC cohorts, the third tertile of urine lactate/creatinine was associated with more rapid estimated glomerular filtration rate decline, relative to first tertile. Patients with T1D demonstrated a strong association between glucose and lactate in both plasma and urine. Glucose-stimulated lactate likely derives in part from proximal tubular cells, since lactate production was attenuated with sodium-glucose cotransporter-2 (SGLT2) inhibition in kidney sections and in SGLT2-deficient mice. Several glycolytic genes were elevated in human diabetic proximal tubules. Lactate levels above 2.5 mM potently inhibited mitochondrial oxidative phosphorylation in human proximal tubule (HK2) cells. We conclude that increased lactate production under diabetic conditions can contribute to mitochondrial dysfunction and become a feed-forward component to DKD pathogenesis.