Open research questions in Hyperglycemia and glycemic control in critically ill and hospitalized patients

What the literature leaves open

• Continuous glucose monitoring (CGM) provides real‐time glucose trend information; however, its clinical utility during paediatric DKA management in the intensive care unit (ICU) remains uncertain.

  Continuous Glucose Monitoring and Hypoglycaemia Risk During Paediatric <scp>DKA</scp> Treatment in the <scp>PICU</scp> : A Retrospective Cohort Study · 2026 · DOI

• The current study has several limitations which should be considered with due attention. The first limi- tation is the small sample size (n = 50), which by itself interferes with the statistical power of our analyses and increases the risk of both type 1 errors (false positives due to chance findings), and type 2 error (false nega- tives due to insufficient power). There was no formal calculation of power and therefore, the results ought to be considered as exploratory. Second, the cross-sec- tional design does not allow us to establish a causality; we only report relationships but not predictive relation- ships. The research would need to be conducted in a longitudinal study to determine whether the hemato- logical parameter changes happen before or after the change in the glycemic control. Third, despite the use of exclusion criteria, it is possible that undetermined of- fending factors, including nutritional status (e.g., iron, vitamin B12, and folate levels), smoking history, and physical activity levels, use of certain oral hypoglycemic agents or insulin regimens, and presence of undeter- mined subclinical conditions could have affected hema- tological parameters and glycemic control [24]. Finally, given the exploratory nature of this study, several statistical comparisons were performed with- out adjusting them formally adjustment multiple test (such as the Bonferonni correction), which increases the probability of type I error. Therefore, the results particularly those of borderline significance must be in- terpreted with caution, and require replication in inde- pendent cohorts [25]. CONCLUSION In this exploratory study, patients with poor glyce- mic control exhibited significantly higher values of WBC, neutrophil, and platelet counts, as well as, an in- creased MPV, compared to the good glycemic control group. Notably, platelets count showed moderate posi- tive correlations with the levels of HbA1c. On the other hand, RBC indices were statistically similar across the cohorts. These findings suggest that platelet activation and severity of glycemic dysregulation in T2DM are as- sociated with inflammatory markers. The results sug- gest a relationship between inflammatory and throm- bocytic parameters and glycemic control status, but the small sample size of the study, the use of cross-section- al design, and the likelihood of unmeasured confound- ing lead to the conclusion that the results are hypothe- sis-generating as opposed to conclusive. To confirm such associations, clarify the underlying processes, de- fine the temporal relation, and also if these easily ob- tainable hematological measures have clinical value in the management of diabetes mellitus or whether they are useful in stratifying risk of diabetic complications, larger, prospective cohort studies are necessary.

  Correlation of complete blood count parameters with glycemic control in type 2 diabetes mellitus · 2026 · DOI

• Furthermore, the findings underline the need for individualized insulin approaches, which may be as- sociated with better glycemic outcomes in these set- tings, warranting further investigation rather than immediate practice-changing conclusions, while con- tributing to the development of the concept of insulin stewardship in India.

  Glycemic management in critically ill and surgical patients with type 2 diabetes: safety signals and medication-related problems in a hospital-based study · 2026 · DOI

• Limitations include lack of baseline patient characteristics prior to insulin therapy initiation, absence of long-term follow-up, and variability in insulin protocols across centers. Additionally, the use of RBS as the primary glycemic outcome does not capture glycemic variability Romanian medical JouRnal – Volume 73, no. 1, 2026 94 or time-in-range, which are increasingly recognized as important metrics. Overall, these results highlight an ongoing challenge in balancing the benefits of strict glucose control against the risks of hypoglycemia in surgical and critically ill patients with T2DM. While some evidence favors moderate glycemic targets (<140 mg/dL) to prevent complications such as wound infections and myocardial events, increased rates of hypoglycemia with intensive regimens support the need for individualized targets based on patient risk [19–25]. The study also demonstrates the value of standardized approaches such as the PCNE classification and interdisciplinary, pharmacist-led interventions in optimizing drug therapy, particularly in complex tertiary care settings where clinician time is limited. Future large-scale, multicenter research could help define optimal glycemic targets for different patient groups and reinforce the role of clinical pharmacists in supporting best practices in glycemic management in Indian hospitals. This study did not include formal measures of illness severity such as APACHE II or SOFA scores, nor surrogate clinical indicators of disease severity. As a result, differences in baseline severity between critically ill and surgical patients, as well as between those receiving intensive insulin therapy and liberal insulin therapy, could not be accounted for. This may have influenced glycemic outcomes and the occurrence of drug-related problems, thus limiting a definitive causal interpretation of between-group comparisons. coNcLuSIoN The present study emphasizes the importance of ensuring adequate glycemic control in critically ill and surgical patients in India. Given its observational nature, the findings highlight patterns and associations in glycemic management rather than establishing causal relationships. From this analysis, it can be observed that timely insulin titration and monitoring were associated with improved glycemic control in critically ill patients with T2DM without a disproportionate increase in hypoglycemia; however, these observations do not confirm the effectiveness or safety of specific insulin strategies.

  Glycemic management in critically ill and surgical patients with type 2 diabetes: safety signals and medication-related problems in a hospital-based study · 2026 · DOI

• Abstract Background The leuko‐glycemic index (LGI) has been suggested as a possible prognostic marker for Acute coronary syndrome (ACS) but, its predictive capacity for mortality, especially among individuals with diabetes, remains poorly understood.

  The role of leuko‐glycemic index in predicting 30‐day mortality in diabetic and non‐diabetic patients with acute coronary syndrome · 2026 · DOI

• In India, the true burden of CHI remains uncertain due to limited awareness, diagnostic delays, fragmented care pathways and restricted access specialised centers compounded by the absence of a national surveillance system.

  Molecular Genetic Spectrum and Clinical Correlates of Congenital Hyperinsulinism in India: A Multicentric Cross-sectional Study · 2026 · DOI

• Current therapeutic evidence remains limited: dichloroacetic acid reduces serum lactate by 20-30% but shows no proven survival benefit; GPR81 modulators remain in development; GM-CSF may increase HLA-DR expression but demonstrates inconsistent effects on infection and mortality.

  Transcending metabolic acidosis: lactate as an epigenetic signal reprogramming diabetes-sepsis immunity · 2026 · DOI

• The present study was conducted in tertiary care hospitals; its findings may not fully represent practices in secondary or rural healthcare settings. Although the final sample size was slightly below the calculated target, post hoc analysis indicated adequate statistical power. However, failing to reach the initial sample target may introduce non-response bias, potentially limiting the representativeness of the findings across all Turkish ICU settings. The use of self-reported data introduces potential recall bias; however, this limitation was mitigated through a structured survey design and validation. Future studies should incorporate objective audits and include a broader range of healthcare institutions. CONCLUSION Glycemic management practices in Turkish ICUs exhibit substantial heterogeneity, influenced by institutional resources, physician specialty, and limited use of HbA1c testing and CGM. University hospitals exhibit higher protocol adherence, whereas public hospitals face resource-related challenges. Implementing standardized national protocols, multidisciplinary training programs, and pilot CGM initiatives may improve alignment with international guidelines and enhance patient outcomes in Türkiye’s ICUs.

  Glycemic Control Practices in Intensive Care Units: A National Survey Study · 2026 · DOI

• This study has some limitations that should be taken into consideration when interpreting the study's results and implications.  The presence of confounding variables (e.g., patient stress, postoperative pain management, etc.) that could influence blood glucose levels and affect the outcomes.  Time-dependent changes, as the blood glucose levels can vary throughout the day due to circadian rhythms, might not be fully accounted for in the study design.

  EFFECT OF SPINAL ANESTHESIA COMPARED TO GENERAL ANESTHESIA ON THE LEVEL OF BLOOD GLUCOSE IN PATIENTS UNDERGOING LOWER ABDOMINAL SURGERY · 2026 · DOI

• Conclusion: PGH after gastrectomy for gastric cancer is an underrecognized but clinically meaningful metabolic disturbance.

  Mechanistic insights, clinical significance, and management strategies for postgastrectomy hypoglycemia in gastric cancer patients in the era of continuous glucose monitoring: a narrative review · 2026 · DOI

• Some aspects of man- agement show critical issues when compared with the inter- national literature, particularly where recommendations are scarce or not comprehensive across clinical contexts.

  Knowledge, attitudes, and practices in pediatric hypoglycemia in Italy (KAPPHy study) · 2026 · DOI

• This finding underscores the lack of consensus currently surrounding the definition of hypoglycemia beyond the neonatal period and highlights the need for harmonized guidance.

  Knowledge, attitudes, and practices in pediatric hypoglycemia in Italy (KAPPHy study) · 2026 · DOI

• Aboriginal and Torres Strait Islander people have higher rates of diabetes mellitus and post‐operative complications than non‐Indigenous Australians, yet data on their perioperative glycaemic profiles are lacking.

  Perioperative glycaemic profiles in Aboriginal and Torres Strait Islander people with diabetes mellitus · 2026 · DOI

• As insulinoma is a rare phenomenon with an unpredictable clinical course, current reportings regarding the anaesthetic management of patients with this pathology are relatively lacking.

  Perioperative glycemia regulation for insulinoma surgery - challenges faced by the anaesthesiologist: A case report · 2025 · DOI

• A further investigation of the emergency department endocrinology consultations in detail will contribute to detecting the problems in this process and; therefore, its improvement.

  Endocrinology Consultations Evaluated in the Emergency Department over the Last Five Years: A Single Center Experience · 2023 · DOI

• Such patients should be investigated for the presence of a prediabetic status or an underlying disease that can trigger a hyper or hypoglycemic episode.

  Analysis of Emergency Department Admissions with Hypo or Hyperglycemia in the Month of Ramadan · 2021 · DOI

• Little is known about the prevalence of insulin administration errors in hospitals, especially in resource-restricted settings, where the burden of diabetes is growing alarmingly.

  Errors in Preparation and Administration of Insulin in Two Urban Vietnamese Hospitals · 2013 · DOI

Most-cited papers in Hyperglycemia and glycemic control in critically ill and hospitalized patients

• Intensive versus Conventional Glucose Control in Critically Ill Patients · New England Journal of Medicine · 2009 · 4,074 citations
• Glucose Control and Vascular Complications in Veterans with Type 2 Diabetes · New England Journal of Medicine · 2008 · 3,898 citations
• Intensive Insulin Therapy and Pentastarch Resuscitation in Severe Sepsis · New England Journal of Medicine · 2008 · 2,348 citations
• Hyperglycemic Crises in Urban Blacks · Archives of Internal Medicine · 1997 · 272 citations
• The prognostic value of the stress hyperglycemia ratio for all-cause and cardiovascular mortality in patients with diabetes or prediabetes: insights from NHANES 2005–2018 · Cardiovascular Diabetology · 2024 · 111 citations
• Association between stress hyperglycemia ratio index and all-cause mortality in critically ill patients with atrial fibrillation: a retrospective study using the MIMIC-IV database · Cardiovascular Diabetology · 2024 · 63 citations
• Point-of-care testing for patients with diabetes, hyperlipidaemia or coagulation disorders in the general practice setting: a systematic review · Family Practice · 2009 · 43 citations
• Glycemia management in acute ischemic stroke: current concepts and novel therapeutic targets · Postgraduate Medicine · 2019 · 34 citations
• Intensive glucose control during the perioperative period for diabetic patients undergoing surgery: An updated systematic review and meta-analysis · Journal of Clinical Anesthesia · 2021 · 26 citations
• Frequent and severe hypoglycaemia detected with continuous glucose monitoring in older institutionalised patients with diabetes · Age and Ageing · 2021 · 24 citations

Most recent work

• Associations between GLP 1 receptor agonist therapy and surgical wound healing in a high-risk cohort · medRxiv · 2026
• Prognostic value of stress hyperglycemia ratio in critically Ill patients with acute kidney injury: a machine learning-driven retrospective cohort analysis · Health Information Science and Systems · 2026
• Post-surgical DKA stems from poor glycemic control prior to surgery and perioperative catecholamine usage: unmatched case–control study · Perioperative Medicine · 2026
• Hypoglycemic Events Focusing on Situational Factors, Bystander Identification, and Prehospital Management · Journal of Clinical Medicine · 2026
• Changing trends and variation in service delivery for inpatient diabetes care in England: A national survey · Diabetic Medicine · 2026
• Improving diagnostic accuracy of 72-hour supervised fasting test for hypoglycemia evaluation: A quality improvement project · World Journal of Methodology · 2026
• Reliability of point-of-care glucose in neonates: revisiting hypoglycemia protocols in the NICU · Journal of Pediatric Endocrinology and Metabolism · 2026
• Association of glycated hemoglobin levels with 3-year mortality in hospitalized older adults with diabetes: The role of frailty · World Journal of Clinical Cases · 2026
• Association of stress hyperglycemia ratio with 1-year all-cause mortality in patients with acute myocardial infarction and chronic kidney disease: a retrospective two-cohort study · European Journal of Medical Research · 2026
• Comparative prognostic value of TyG index and TyG-BMI for 90-day all-cause mortality in critically ill older adults with ASCVD: a machine learning analysis of the MIMIC-IV database · Cardiovascular Diabetology · 2026

Related topics in Medicine